diff --git a/lib/galaxy/config/__init__.py b/lib/galaxy/config/__init__.py
index 8fdef452fdc..eee53c0850e 100644
--- a/lib/galaxy/config/__init__.py
+++ b/lib/galaxy/config/__init__.py
@@ -422,7 +422,7 @@ class CommonConfigurationMixin:
 
     def is_admin_user(self, user):
         """Determine if the provided user is listed in `admin_users`."""
-        return user is not None and user.email in self.admin_users_list
+        return user and (user.email in self.admin_users_list or user.bootstrap_admin_user)
 
     @property
     def sentry_dsn_public(self):
diff --git a/lib/galaxy/managers/context.py b/lib/galaxy/managers/context.py
index 6c9725ace0e..d927316571e 100644
--- a/lib/galaxy/managers/context.py
+++ b/lib/galaxy/managers/context.py
@@ -103,13 +103,13 @@ class ProvidesUserContext:
     """ For transaction-like objects to provide Galaxy convience layer for
     reasoning about users.
 
-    Mixed in class must provide `user`, `api_inherit_admin`, and `app`
+    Mixed in class must provide `user` and `app`
     properties.
     """
 
     @property
     def anonymous(self):
-        return self.user is None and not self.api_inherit_admin
+        return self.user is None
 
     def get_current_user_roles(self):
         user = self.user
@@ -121,7 +121,7 @@ class ProvidesUserContext:
 
     @property
     def user_is_admin(self):
-        return self.api_inherit_admin or self.app.config.is_admin_user(self.user)
+        return self.app.config.is_admin_user(self.user)
 
     @property
     def user_can_do_run_as(self):
@@ -130,7 +130,7 @@ class ProvidesUserContext:
             return False
         user_in_run_as_users = self.user and self.user.email in run_as_users
         # Can do if explicitly in list or master_api_key supplied.
-        can_do_run_as = user_in_run_as_users or self.api_inherit_admin
+        can_do_run_as = user_in_run_as_users or self.user.bootstrap_admin_user
         return can_do_run_as
 
     @property
diff --git a/lib/galaxy/managers/users.py b/lib/galaxy/managers/users.py
index 0a51c99f1f7..0236a353679 100644
--- a/lib/galaxy/managers/users.py
+++ b/lib/galaxy/managers/users.py
@@ -1,6 +1,7 @@
 """
 Manager and Serializer for Users.
 """
+import hashlib
 import logging
 import random
 import socket
@@ -14,7 +15,8 @@ from sqlalchemy.orm.exc import NoResultFound
 from galaxy import (
     exceptions,
     model,
-    util
+    schema,
+    util,
 )
 from galaxy.managers import (
     api_keys,
@@ -239,6 +241,8 @@ class UserManager(base.ModelManager, deletable.PurgableManagerMixin):
         try:
             provided_key = sa_session.query(self.app.model.APIKeys).filter(self.app.model.APIKeys.table.c.key == api_key).one()
         except NoResultFound:
+            if self.check_master_api_key(api_key=api_key):
+                return schema.BoostrapAdminUser()
             raise exceptions.AuthenticationFailed('Provided API key is not valid.')
         if provided_key.user.deleted:
             raise exceptions.AuthenticationFailed('User account is deactivated, please contact an administrator.')
@@ -247,6 +251,15 @@ class UserManager(base.ModelManager, deletable.PurgableManagerMixin):
             raise exceptions.AuthenticationFailed('Provided API key has expired.')
         return provided_key.user
 
+    def check_master_api_key(self, api_key):
+        master_api_key = getattr(self.app.config, 'master_api_key', None)
+        if not master_api_key:
+            return False
+        # Hash keys to make them the same size, so we can do safe comparison.
+        master_hash = hashlib.sha256(util.smart_str(master_api_key)).hexdigest()
+        provided_hash = hashlib.sha256(util.smart_str(api_key)).hexdigest()
+        return util.safe_str_cmp(master_hash, provided_hash)
+
     # ---- admin
     def is_admin(self, user, trans=None):
         """Return True if this user is an admin (or session is authenticated as admin).
diff --git a/lib/galaxy/model/__init__.py b/lib/galaxy/model/__init__.py
index 862f6ae4b46..edb4ed85961 100644
--- a/lib/galaxy/model/__init__.py
+++ b/lib/galaxy/model/__init__.py
@@ -356,6 +356,7 @@ class JobLike:
 
 class User(Dictifiable, RepresentById):
     use_pbkdf2 = True
+    bootstrap_admin_user = False
     """
     Data for a Galaxy user or admin and relations to their
     histories, credentials, and roles.
diff --git a/lib/galaxy/schema/__init__.py b/lib/galaxy/schema/__init__.py
index e69de29bb2d..3d4e3131f80 100644
--- a/lib/galaxy/schema/__init__.py
+++ b/lib/galaxy/schema/__init__.py
@@ -0,0 +1,12 @@
+import typing
+
+from pydantic import BaseModel
+
+
+class BoostrapAdminUser(BaseModel):
+    id = 0
+    email: typing.Optional[str] = None
+    bootstrap_admin_user = True
+
+    def all_roles(*args) -> list:
+        return []
diff --git a/lib/galaxy/web/framework/decorators.py b/lib/galaxy/web/framework/decorators.py
index d13a4b7a0e5..24db7570752 100644
--- a/lib/galaxy/web/framework/decorators.py
+++ b/lib/galaxy/web/framework/decorators.py
@@ -161,7 +161,6 @@ def legacy_expose_api(func, to_json=True, user_required=True):
                 return "Malformed user id ( %s ) specified, unable to decode." % str(kwargs['payload']['run_as'])
             try:
                 user = trans.sa_session.query(trans.app.model.User).get(decoded_user_id)
-                trans.api_inherit_admin = trans.user_is_admin
                 trans.set_user(user)
             except Exception:
                 trans.response.status = 400
@@ -286,7 +285,6 @@ def expose_api(func, to_json=True, user_required=True, user_or_session_required=
                 return __api_error_response(trans, err_code=error_code, err_msg=error_message, status_code=400)
             try:
                 user = trans.sa_session.query(trans.app.model.User).get(decoded_user_id)
-                trans.api_inherit_admin = trans.user_is_admin
                 trans.set_user(user)
             except Exception:
                 error_code = error_codes.USER_INVALID_RUN_AS
diff --git a/lib/galaxy/webapps/base/webapp.py b/lib/galaxy/webapps/base/webapp.py
index d96b8a26b26..5f8b6ba04b5 100644
--- a/lib/galaxy/webapps/base/webapp.py
+++ b/lib/galaxy/webapps/base/webapp.py
@@ -1,7 +1,6 @@
 """
 """
 import datetime
-import hashlib
 import inspect
 import logging
 import os
@@ -33,8 +32,6 @@ from galaxy.managers.users import UserManager
 from galaxy.util import (
     asbool,
     safe_makedirs,
-    safe_str_cmp,
-    smart_str,
     unicodify
 )
 from galaxy.util.sanitize_html import sanitize_html
@@ -204,8 +201,6 @@ class GalaxyWebTransaction(base.DefaultWebTransaction,
         # that the current history should not be used for parameter values
         # and such).
         self.workflow_building_mode = False
-        # Flag indicating whether this is an API call and the API key user is an administrator
-        self.api_inherit_admin = False
         self.__user = None
         self.galaxy_session = None
         self.error_message = None
@@ -362,9 +357,10 @@ class GalaxyWebTransaction(base.DefaultWebTransaction,
     def set_user(self, user):
         """Set the current user."""
         if self.galaxy_session:
-            self.galaxy_session.user = user
-            self.sa_session.add(self.galaxy_session)
-            self.sa_session.flush()
+            if user.bootstrap_admin_user:
+                self.galaxy_session.user = user
+                self.sa_session.add(self.galaxy_session)
+                self.sa_session.flush()
         self.__user = user
 
     user = property(get_user, set_user)
@@ -407,12 +403,7 @@ class GalaxyWebTransaction(base.DefaultWebTransaction,
         api_key = self.request.params.get('key', None) or self.request.headers.get('x-api-key', None)
         secure_id = self.get_cookie(name=session_cookie)
         api_key_supplied = self.environ.get('is_api_request', False) and api_key
-        if api_key_supplied and self._check_master_api_key(api_key):
-            self.api_inherit_admin = True
-            log.info("Session authenticated using Galaxy master api key")
-            self.user = None
-            self.galaxy_session = None
-        elif api_key_supplied:
+        if api_key_supplied:
             # Sessionless API transaction, we just need to associate a user.
             try:
                 user = self.user_manager.by_api_key(api_key)
@@ -434,15 +425,6 @@ class GalaxyWebTransaction(base.DefaultWebTransaction,
             self.user = None
             self.galaxy_session = None
 
-    def _check_master_api_key(self, api_key):
-        master_api_key = getattr(self.app.config, 'master_api_key', None)
-        if not master_api_key:
-            return False
-        # Hash keys to make them the same size, so we can do safe comparison.
-        master_hash = hashlib.sha256(smart_str(master_api_key)).hexdigest()
-        provided_hash = hashlib.sha256(smart_str(api_key)).hexdigest()
-        return safe_str_cmp(master_hash, provided_hash)
-
     def _ensure_valid_session(self, session_cookie, create=True):
         """
         Ensure that a valid Galaxy session exists and is available as
diff --git a/lib/galaxy/webapps/galaxy/api/users.py b/lib/galaxy/webapps/galaxy/api/users.py
index 8bc5028510d..42246cc6256 100644
--- a/lib/galaxy/webapps/galaxy/api/users.py
+++ b/lib/galaxy/webapps/galaxy/api/users.py
@@ -222,7 +222,7 @@ class UserAPIController(BaseAPIController, UsesTagsMixin, CreatesApiKeysMixin, B
 
         # only allow updating other users if they're admin
         editing_someone_else = current_user != user_to_update
-        is_admin = trans.api_inherit_admin or self.user_manager.is_admin(current_user)
+        is_admin = self.user_manager.is_admin(current_user)
         if editing_someone_else and not is_admin:
             raise exceptions.InsufficientPermissionsException('You are not allowed to update that user', id=id)
 
diff --git a/lib/galaxy/work/context.py b/lib/galaxy/work/context.py
index cc5d88c6b95..64a4333ab0b 100644
--- a/lib/galaxy/work/context.py
+++ b/lib/galaxy/work/context.py
@@ -24,7 +24,6 @@ class WorkRequestContext(ProvidesAppContext, ProvidesUserContext, ProvidesHistor
         self.__user = user
         self.__user_current_roles = None
         self.__history = history
-        self.api_inherit_admin = False
         self.workflow_building_mode = workflow_building_mode
 
     def get_history(self, create=False):
diff --git a/lib/tool_shed/webapp/model/__init__.py b/lib/tool_shed/webapp/model/__init__.py
index d3ab82470bb..cbfad8f11be 100644
--- a/lib/tool_shed/webapp/model/__init__.py
+++ b/lib/tool_shed/webapp/model/__init__.py
@@ -33,6 +33,7 @@ class APIKeys:
 class User(Dictifiable):
     dict_collection_visible_keys = ['id', 'username']
     dict_element_visible_keys = ['id', 'username']
+    bootstrap_admin_user = False
 
     def __init__(self, email=None, password=None):
         self.email = email
diff --git a/test/unit/unittest_utils/galaxy_mock.py b/test/unit/unittest_utils/galaxy_mock.py
index b0513375184..cbcfe489a16 100644
--- a/test/unit/unittest_utils/galaxy_mock.py
+++ b/test/unit/unittest_utils/galaxy_mock.py
@@ -211,6 +211,7 @@ class MockTrans:
         self.error_message = None
         self.anonymous = False
         self.debug = True
+        self.user_is_admin = False
 
         self.galaxy_session = None
         self.__user = user