diff --git a/CHANGES.rst b/CHANGES.rst
index 91439096..d302347f 100644
--- a/CHANGES.rst
+++ b/CHANGES.rst
@@ -16,6 +16,10 @@ Unreleased
 
 -   Refactor ``register_error_handler`` to consolidate error checking.
     Rewrite some error messages to be more consistent. :issue:`4559`
+-   Use Blueprint decorators and functions intended for setup after
+    registering the blueprint will show a warning. In the next version,
+    this will become an error just like the application setup methods.
+    :issue:`4571`
 
 
 Version 2.1.2
diff --git a/src/flask/blueprints.py b/src/flask/blueprints.py
index c801d1b4..e4a9a5ce 100644
--- a/src/flask/blueprints.py
+++ b/src/flask/blueprints.py
@@ -162,7 +162,6 @@ class Blueprint(Scaffold):
     .. versionadded:: 0.7
     """
 
-    warn_on_modifications = False
     _got_registered_once = False
 
     #: Blueprint local JSON encoder class to use. Set to ``None`` to use
@@ -209,7 +208,7 @@ class Blueprint(Scaffold):
         self._blueprints: t.List[t.Tuple["Blueprint", dict]] = []
 
     def _is_setup_finished(self) -> bool:
-        return self.warn_on_modifications and self._got_registered_once
+        return self._got_registered_once
 
     def record(self, func: t.Callable) -> None:
         """Registers a function that is called when the blueprint is
@@ -217,14 +216,15 @@ class Blueprint(Scaffold):
         state as argument as returned by the :meth:`make_setup_state`
         method.
         """
-        if self._got_registered_once and self.warn_on_modifications:
+        if self._got_registered_once:
+            # TODO: Upgrade this to an error and unify it setupmethod in 2.3
             from warnings import warn
 
             warn(
                 Warning(
                     "The blueprint was already registered once but is"
                     " getting modified now. These changes will not show"
-                    " up."
+                    " up.\n This warning will be become an exception in 2.3."
                 )
             )
         self.deferred_functions.append(func)
diff --git a/src/flask/scaffold.py b/src/flask/scaffold.py
index 10e77bbc..b2dd46f3 100644
--- a/src/flask/scaffold.py
+++ b/src/flask/scaffold.py
@@ -27,8 +27,8 @@ from .typing import URLDefaultCallable
 from .typing import URLValuePreprocessorCallable
 
 if t.TYPE_CHECKING:  # pragma: no cover
-    from .wrappers import Response
     from .typing import ErrorHandlerCallable
+    from .wrappers import Response
 
 # a singleton sentinel value for parameter defaults
 _sentinel = object()
@@ -411,6 +411,7 @@ class Scaffold:
         """
         return self._method_route("PATCH", rule, options)
 
+    @setupmethod
     def route(self, rule: str, **options: t.Any) -> t.Callable[[F], F]:
         """Decorate a view function to register it with the given URL
         rule and options. Calls :meth:`add_url_rule`, which has more
@@ -510,6 +511,7 @@ class Scaffold:
         """
         raise NotImplementedError
 
+    @setupmethod
     def endpoint(self, endpoint: str) -> t.Callable:
         """Decorate a view function to register it for the given
         endpoint. Used if a rule is added without a ``view_func`` with