diff --git a/compose.yml b/compose.yml
index 0388699fb5..28a54515c1 100644
--- a/compose.yml
+++ b/compose.yml
@@ -8,6 +8,7 @@ services:
     ports:
       - "8080:8080"
     environment:
-      BUTLER_SERVER_CONFIG_URI: "/butler_root"
+      DAF_BUTLER_REPOSITORY_INDEX: "/butler_config/repository_index.yaml"
     volumes:
       - ../ci_hsc_gen3/DATA:/butler_root
+      - ./docker/compose_files:/butler_config
diff --git a/docker/compose_files/repository_index.yaml b/docker/compose_files/repository_index.yaml
new file mode 100644
index 0000000000..5690de63dd
--- /dev/null
+++ b/docker/compose_files/repository_index.yaml
@@ -0,0 +1 @@
+hsc_gen3: /butler_root
diff --git a/python/lsst/daf/butler/remote_butler/server/_config.py b/python/lsst/daf/butler/remote_butler/server/_config.py
deleted file mode 100644
index 9181fb40c1..0000000000
--- a/python/lsst/daf/butler/remote_butler/server/_config.py
+++ /dev/null
@@ -1,50 +0,0 @@
-# This file is part of daf_butler.
-#
-# Developed for the LSST Data Management System.
-# This product includes software developed by the LSST Project
-# (http://www.lsst.org).
-# See the COPYRIGHT file at the top-level directory of this distribution
-# for details of code ownership.
-#
-# This software is dual licensed under the GNU General Public License and also
-# under a 3-clause BSD license. Recipients may choose which of these licenses
-# to use; please see the files gpl-3.0.txt and/or bsd_license.txt,
-# respectively.  If you choose the GPL option then the following text applies
-# (but note that there is still no warranty even if you opt for BSD instead):
-#
-# This program is free software: you can redistribute it and/or modify
-# it under the terms of the GNU General Public License as published by
-# the Free Software Foundation, either version 3 of the License, or
-# (at your option) any later version.
-#
-# This program is distributed in the hope that it will be useful,
-# but WITHOUT ANY WARRANTY; without even the implied warranty of
-# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
-# GNU General Public License for more details.
-#
-# You should have received a copy of the GNU General Public License
-# along with this program.  If not, see <http://www.gnu.org/licenses/>.
-
-import os
-from dataclasses import dataclass
-
-__all__ = ("Config", "get_config_from_env")
-
-
-@dataclass(frozen=True)
-class Config:
-    """Simplified configuration for a client/server connection."""
-
-    config_uri: str
-    """URI of the configuration."""
-
-
-def get_config_from_env() -> Config:
-    """Retrieve a configuration from the environment."""
-    config_uri = os.getenv("BUTLER_SERVER_CONFIG_URI")
-    if config_uri is None:
-        raise Exception(
-            "The environment variable BUTLER_SERVER_CONFIG_URI "
-            "must point to a Butler configuration to be used by the server"
-        )
-    return Config(config_uri=config_uri)
diff --git a/python/lsst/daf/butler/remote_butler/server/_dependencies.py b/python/lsst/daf/butler/remote_butler/server/_dependencies.py
index ec0cb7986c..075d5f5b72 100644
--- a/python/lsst/daf/butler/remote_butler/server/_dependencies.py
+++ b/python/lsst/daf/butler/remote_butler/server/_dependencies.py
@@ -25,24 +25,34 @@
 # You should have received a copy of the GNU General Public License
 # along with this program.  If not, see <http://www.gnu.org/licenses/>.
 
-from functools import cache
+from typing import Annotated
 
-from lsst.daf.butler import Butler
-from lsst.daf.butler.direct_butler import DirectButler
+from fastapi import Depends
+from lsst.daf.butler import LabeledButlerFactory
 
-from ._config import get_config_from_env
 from ._factory import Factory
 
+_butler_factory = LabeledButlerFactory()
 
-@cache
-def _make_global_butler() -> DirectButler:
-    config = get_config_from_env()
-    butler = Butler.from_config(config.config_uri)
-    if not isinstance(butler, DirectButler):
-        raise TypeError("Server can only use a DirectButler")
-    return butler
 
+async def butler_factory_dependency() -> LabeledButlerFactory:
+    """Return a global LabeledButlerFactory instance.  This will be used to
+    construct internal DirectButler instances for interacting with the Butler
+    repositories we are serving.
+    """
+    return _butler_factory
 
-def factory_dependency() -> Factory:
-    """Return factory dependency for injection into FastAPI."""
-    return Factory(butler=_make_global_butler())
+
+async def factory_dependency(
+    repository: str, butler_factory: Annotated[LabeledButlerFactory, Depends(butler_factory_dependency)]
+) -> Factory:
+    """Return Factory object for injection into FastAPI.
+
+    Parameters
+    ----------
+    repository : `str`
+        Label of the repository for lookup from the repository index.
+    butler_factory : `LabeledButlerFactory`
+        Factory for instantiating DirectButlers.
+    """
+    return Factory(butler_factory=butler_factory, repository=repository)
diff --git a/python/lsst/daf/butler/remote_butler/server/_factory.py b/python/lsst/daf/butler/remote_butler/server/_factory.py
index 06c52b8f69..8994fac7fb 100644
--- a/python/lsst/daf/butler/remote_butler/server/_factory.py
+++ b/python/lsst/daf/butler/remote_butler/server/_factory.py
@@ -25,22 +25,30 @@
 # You should have received a copy of the GNU General Public License
 # along with this program.  If not, see <http://www.gnu.org/licenses/>.
 
+from lsst.daf.butler import LabeledButlerFactory
 from lsst.daf.butler.direct_butler import DirectButler
 
 __all__ = ("Factory",)
 
 
 class Factory:
-    """Class to provide a cached Butler instance.
+    """Class for instantiating per-request dependencies, following the pattern
+    in `SQR-072 <https://sqr-072.lsst.io/>`_.
 
     Parameters
     ----------
-    butler : `DirectButler`
-        Butler to use.
+    repository : `str`
+        The label of the Butler repository requested by the user.
+    butler_factory : `LabeledButlerFactory`
+        Factory used to instantiate Butler instances.
     """
 
-    def __init__(self, *, butler: DirectButler):
-        self._butler = butler
+    def __init__(self, *, repository: str, butler_factory: LabeledButlerFactory):
+        self._repository = repository
+        self._butler_factory = butler_factory
 
     def create_butler(self) -> DirectButler:
-        return self._butler
+        butler = self._butler_factory.create_butler(label=self._repository, access_token=None)
+        if not isinstance(butler, DirectButler):
+            raise TypeError("Server can only use a DirectButler")
+        return butler
diff --git a/python/lsst/daf/butler/remote_butler/server/_server.py b/python/lsst/daf/butler/remote_butler/server/_server.py
index 5a0329e4df..6759b00fbb 100644
--- a/python/lsst/daf/butler/remote_butler/server/_server.py
+++ b/python/lsst/daf/butler/remote_butler/server/_server.py
@@ -45,7 +45,12 @@
 
 app = FastAPI()
 app.add_middleware(GZipMiddleware, minimum_size=1000)
-app.include_router(external_router, prefix=_DEFAULT_API_PATH)
+
+# A single instance of the server can serve data from multiple Butler
+# repositories.  This 'repository' path placeholder is consumed by
+# factory_dependency().
+repository_placeholder = "{repository}"
+app.include_router(external_router, prefix=f"{_DEFAULT_API_PATH}/repo/{repository_placeholder}")
 
 
 @app.exception_handler(MissingDatasetTypeError)
diff --git a/tests/test_server.py b/tests/test_server.py
index 49d38db0c4..eace355d0e 100644
--- a/tests/test_server.py
+++ b/tests/test_server.py
@@ -36,8 +36,8 @@
     from fastapi.testclient import TestClient
     from lsst.daf.butler.remote_butler import RemoteButler, RemoteButlerFactory
     from lsst.daf.butler.remote_butler._authentication import _EXPLICIT_BUTLER_ACCESS_TOKEN_ENVIRONMENT_KEY
-    from lsst.daf.butler.remote_butler.server import Factory, app
-    from lsst.daf.butler.remote_butler.server._dependencies import factory_dependency
+    from lsst.daf.butler.remote_butler.server import app
+    from lsst.daf.butler.remote_butler.server._dependencies import butler_factory_dependency
     from lsst.resources.s3utils import clean_test_environment_for_s3, getS3Client
     from moto import mock_s3
 except ImportError:
@@ -70,6 +70,8 @@
 
 TESTDIR = os.path.abspath(os.path.dirname(__file__))
 
+TEST_REPOSITORY_NAME = "testrepo"
+
 
 def _make_test_client(app, raise_server_exceptions=True):
     client = TestClient(app, raise_server_exceptions=raise_server_exceptions)
@@ -80,7 +82,7 @@ def _make_remote_butler(http_client, *, collections: str | None = None):
     options = None
     if collections is not None:
         options = ButlerInstanceOptions(collections=collections)
-    factory = RemoteButlerFactory("https://test.example/api/butler", http_client)
+    factory = RemoteButlerFactory(f"https://test.example/api/butler/repo/{TEST_REPOSITORY_NAME}", http_client)
     return factory.create_butler_for_access_token("fake-access-token", butler_options=options)
 
 
@@ -115,12 +117,9 @@ def setUpClass(cls):
         cls.simple_dataset_ref = _create_simple_dataset(cls.repo.butler)
 
         # Override the server's Butler initialization to point at our test repo
-        server_butler = Butler.from_config(cls.root, writeable=True)
-
-        def create_factory_dependency():
-            return Factory(butler=server_butler)
+        server_butler_factory = LabeledButlerFactory({TEST_REPOSITORY_NAME: cls.root})
 
-        app.dependency_overrides[factory_dependency] = create_factory_dependency
+        app.dependency_overrides[butler_factory_dependency] = lambda: server_butler_factory
 
         # Set up the RemoteButler that will connect to the server
         cls.client = _make_test_client(app)
@@ -140,13 +139,13 @@ def create_factory_dependency():
         # Populate the test server.
         # The DatastoreMock is required because the datasets referenced in
         # these imports do not point at real files.
-        DatastoreMock.apply(server_butler)
-        server_butler.import_(filename=os.path.join(TESTDIR, "data", "registry", "base.yaml"))
-        server_butler.import_(filename=os.path.join(TESTDIR, "data", "registry", "datasets.yaml"))
+        DatastoreMock.apply(cls.repo.butler)
+        cls.repo.butler.import_(filename=os.path.join(TESTDIR, "data", "registry", "base.yaml"))
+        cls.repo.butler.import_(filename=os.path.join(TESTDIR, "data", "registry", "datasets.yaml"))
 
     @classmethod
     def tearDownClass(cls):
-        del app.dependency_overrides[factory_dependency]
+        del app.dependency_overrides[butler_factory_dependency]
         removeTestTempDir(cls.root)
 
     def test_health_check(self):
@@ -154,15 +153,9 @@ def test_health_check(self):
         self.assertEqual(response.status_code, 200)
         self.assertEqual(response.json()["name"], "butler")
 
-    def test_simple(self):
-        response = self.client.get("/api/butler/v1/universe")
-        self.assertEqual(response.status_code, 200)
-        self.assertIn("namespace", response.json())
-
-    def test_remote_butler(self):
+    def test_dimension_universe(self):
         universe = self.butler.dimensions
         self.assertEqual(universe.namespace, "daf_butler")
-        self.assertFalse(self.butler.isWriteable())
 
     def test_get_dataset_type(self):
         bias_type = self.butler.get_dataset_type("bias")
@@ -243,22 +236,24 @@ def test_instantiate_via_butler_http_search(self):
         def override_read(http_resource_path):
             return self.client.get(http_resource_path.geturl()).content
 
+        server_url = f"https://test.example/api/butler/repo/{TEST_REPOSITORY_NAME}/"
+
         with patch.object(HttpResourcePath, "read", override_read):
             # Add access key to environment variables. RemoteButler
             # instantiation will throw an error if access key is not
             # available.
             with mock_env({_EXPLICIT_BUTLER_ACCESS_TOKEN_ENVIRONMENT_KEY: "fake-access-token"}):
                 butler = Butler(
-                    "https://test.example/api/butler",
+                    server_url,
                     collections=["collection1", "collection2"],
                     run="collection2",
                 )
-            butler_factory = LabeledButlerFactory({"server": "https://test.example/api/butler"})
+            butler_factory = LabeledButlerFactory({"server": server_url})
             factory_created_butler = butler_factory.create_butler(label="server", access_token="token")
         self.assertIsInstance(butler, RemoteButler)
         self.assertIsInstance(factory_created_butler, RemoteButler)
-        self.assertEqual(butler._server_url, "https://test.example/api/butler/")
-        self.assertEqual(factory_created_butler._server_url, "https://test.example/api/butler/")
+        self.assertEqual(butler._server_url, server_url)
+        self.assertEqual(factory_created_butler._server_url, server_url)
 
         self.assertEqual(butler.collections, ("collection1", "collection2"))
         self.assertEqual(butler.run, "collection2")
diff --git a/tests_integration/test_docker_container.py b/tests_integration/test_docker_container.py
index 58e638f524..c12e3d31c0 100644
--- a/tests_integration/test_docker_container.py
+++ b/tests_integration/test_docker_container.py
@@ -24,13 +24,20 @@ def _run_server_docker():
 
         port = 8080
         butler_root = "/butler_root"
+
+        # Set up a repository index file to be read in by the server
+        index_filename = "repo_index.yaml"
+        repo_name = "testserver"
+        with open(os.path.join(temp_dir, index_filename), "wb") as fh:
+            fh.write(f"{repo_name}: {butler_root}\n".encode())
+
         docker_image = os.getenv("BUTLER_SERVER_DOCKER_IMAGE")
         if not docker_image:
             raise Exception("BUTLER_SERVER_DOCKER_IMAGE must be set")
         container = (
             DockerContainer(docker_image)
             .with_exposed_ports(port)
-            .with_env("BUTLER_SERVER_CONFIG_URI", butler_root)
+            .with_env("DAF_BUTLER_REPOSITORY_INDEX", f"{butler_root}/{index_filename}")
             .with_volume_mapping(temp_dir, butler_root, "rw")
         )
 
@@ -38,7 +45,7 @@ def _run_server_docker():
             server_host = container.get_container_host_ip()
             server_port = container.get_exposed_port(port)
             server_url = f"http://{server_host}:{server_port}"
-            full_server_url = f"{server_url}/api/butler"
+            full_server_url = f"{server_url}/api/butler/repo/{repo_name}"
             try:
                 _wait_for_startup(server_url)
                 yield full_server_url