diff --git a/CHANGELOG.md b/CHANGELOG.md
index 3fd85a7f6b..ee5ece78bf 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -18,6 +18,8 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - `opentelemetry-instrumentation-aws-lambda` Flush `MeterProvider` at end of function invocation.
   ([#1613](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/1613))
 - Fix aiohttp bug with unset `trace_configs` ([#1592](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/1592))
+- `opentelemetry-instrumentation-django` Allow explicit `excluded_urls` configuration through `instrument()`
+  ([#1618](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/1618))
 
 ### Fixed
 
diff --git a/instrumentation/opentelemetry-instrumentation-django/src/opentelemetry/instrumentation/django/__init__.py b/instrumentation/opentelemetry-instrumentation-django/src/opentelemetry/instrumentation/django/__init__.py
index f683421475..d545a1950b 100644
--- a/instrumentation/opentelemetry-instrumentation-django/src/opentelemetry/instrumentation/django/__init__.py
+++ b/instrumentation/opentelemetry-instrumentation-django/src/opentelemetry/instrumentation/django/__init__.py
@@ -255,9 +255,11 @@ def response_hook(span, request, response):
 from opentelemetry.metrics import get_meter
 from opentelemetry.semconv.metrics import MetricInstruments
 from opentelemetry.trace import get_tracer
+from opentelemetry.util.http import get_excluded_urls, parse_excluded_urls
 
 DJANGO_2_0 = django_version >= (2, 0)
 
+_excluded_urls_from_env = get_excluded_urls("DJANGO")
 _logger = getLogger(__name__)
 
 
@@ -293,6 +295,7 @@ def _instrument(self, **kwargs):
 
         tracer_provider = kwargs.get("tracer_provider")
         meter_provider = kwargs.get("meter_provider")
+        _excluded_urls = kwargs.get("excluded_urls")
         tracer = get_tracer(
             __name__,
             __version__,
@@ -301,6 +304,11 @@ def _instrument(self, **kwargs):
         meter = get_meter(__name__, __version__, meter_provider=meter_provider)
         _DjangoMiddleware._tracer = tracer
         _DjangoMiddleware._meter = meter
+        _DjangoMiddleware._excluded_urls = (
+            _excluded_urls_from_env
+            if _excluded_urls is None
+            else parse_excluded_urls(_excluded_urls)
+        )
         _DjangoMiddleware._otel_request_hook = kwargs.pop("request_hook", None)
         _DjangoMiddleware._otel_response_hook = kwargs.pop(
             "response_hook", None
diff --git a/instrumentation/opentelemetry-instrumentation-django/tests/test_middleware.py b/instrumentation/opentelemetry-instrumentation-django/tests/test_middleware.py
index b4bb33e144..e235c8840e 100644
--- a/instrumentation/opentelemetry-instrumentation-django/tests/test_middleware.py
+++ b/instrumentation/opentelemetry-instrumentation-django/tests/test_middleware.py
@@ -91,6 +91,7 @@
 _django_instrumentor = DjangoInstrumentor()
 
 
+# pylint: disable=too-many-public-methods
 class TestMiddleware(WsgiTestBase):
     @classmethod
     def setUpClass(cls):
@@ -285,6 +286,18 @@ def test_exclude_lists(self):
         span_list = self.memory_exporter.get_finished_spans()
         self.assertEqual(len(span_list), 1)
 
+    def test_exclude_lists_through_instrument(self):
+        _django_instrumentor.uninstrument()
+        _django_instrumentor.instrument(excluded_urls="excluded_explicit")
+        client = Client()
+        client.get("/excluded_explicit")
+        span_list = self.memory_exporter.get_finished_spans()
+        self.assertEqual(len(span_list), 0)
+
+        client.get("/excluded_arg/123")
+        span_list = self.memory_exporter.get_finished_spans()
+        self.assertEqual(len(span_list), 1)
+
     def test_span_name(self):
         # test no query_string
         Client().get("/span_name/1234/")