diff --git a/django/db/models/sql/query.py b/django/db/models/sql/query.py
index 92bfdb1881..6814af6439 100644
--- a/django/db/models/sql/query.py
+++ b/django/db/models/sql/query.py
@@ -1159,6 +1159,9 @@ class Query(object):
         try:
             field, sources, opts, join_list, path = self.setup_joins(
                 parts, opts, alias, can_reuse, allow_many)
+            # split_exclude() needs to know which joins were generated for the
+            # lookup parts
+            self._lookup_joins = join_list
         except MultiJoin as e:
             return self.split_exclude(filter_expr, LOOKUP_SEP.join(parts[:e.level]),
                                       can_reuse, e.names_with_path)
@@ -1899,17 +1902,21 @@ class Query(object):
         for _, paths in names_with_path:
             all_paths.extend(paths)
         contains_louter = False
-        for pos, path in enumerate(all_paths):
+        # Trim and operate only on tables that were generated for
+        # the lookup part of the query. That is, avoid trimming
+        # joins generated for F() expressions.
+        lookup_tables = [t for t in self.tables if t in self._lookup_joins or t == self.tables[0]]
+        for trimmed_paths, path in enumerate(all_paths):
             if path.m2m:
                 break
-            if self.alias_map[self.tables[pos + 1]].join_type == self.LOUTER:
+            if self.alias_map[lookup_tables[trimmed_paths + 1]].join_type == self.LOUTER:
                 contains_louter = True
-            self.unref_alias(self.tables[pos])
+            self.unref_alias(lookup_tables[trimmed_paths])
         # The path.join_field is a Rel, lets get the other side's field
         join_field = path.join_field.field
         # Build the filter prefix.
+        paths_in_prefix = trimmed_paths
         trimmed_prefix = []
-        paths_in_prefix = pos
         for name, path in names_with_path:
             if paths_in_prefix - len(path) < 0:
                 break
@@ -1921,12 +1928,12 @@ class Query(object):
         # Lets still see if we can trim the first join from the inner query
         # (that is, self). We can't do this for LEFT JOINs because we would
         # miss those rows that have nothing on the outer side.
-        if self.alias_map[self.tables[pos + 1]].join_type != self.LOUTER:
+        if self.alias_map[lookup_tables[trimmed_paths + 1]].join_type != self.LOUTER:
             select_fields = [r[0] for r in join_field.related_fields]
-            select_alias = self.tables[pos + 1]
-            self.unref_alias(self.tables[pos])
+            select_alias = lookup_tables[trimmed_paths + 1]
+            self.unref_alias(lookup_tables[trimmed_paths])
             extra_restriction = join_field.get_extra_restriction(
-                self.where_class, None, self.tables[pos + 1])
+                self.where_class, None, lookup_tables[trimmed_paths + 1])
             if extra_restriction:
                 self.where.add(extra_restriction, AND)
         else:
@@ -1934,7 +1941,7 @@ class Query(object):
             # inner query if it happens to have a longer join chain containing the
             # values in select_fields. Lets punt this one for now.
             select_fields = [r[1] for r in join_field.related_fields]
-            select_alias = self.tables[pos]
+            select_alias = lookup_tables[trimmed_paths]
         self.select = [SelectInfo((select_alias, f.column), f) for f in select_fields]
         return trimmed_prefix, contains_louter
 
diff --git a/docs/releases/1.6.5.txt b/docs/releases/1.6.5.txt
index 3c46b953b7..891a688030 100644
--- a/docs/releases/1.6.5.txt
+++ b/docs/releases/1.6.5.txt
@@ -14,3 +14,6 @@ Bugfixes
 
 * Fixed ``pgettext_lazy`` crash when receiving bytestring content on Python 2
   (`#22565 <http://code.djangoproject.com/ticket/22565>`_).
+
+* Fixed the SQL generated when filtering by a negated ``Q`` object that contains
+  a ``F`` object. (`#22429 <http://code.djangoproject.com/ticket/22429>`_).
diff --git a/tests/queries/models.py b/tests/queries/models.py
index 1083968d41..604eed5f07 100644
--- a/tests/queries/models.py
+++ b/tests/queries/models.py
@@ -660,3 +660,18 @@ class Employment(models.Model):
     employer = models.ForeignKey(Company)
     employee = models.ForeignKey(Person)
     title = models.CharField(max_length=128)
+
+
+# Bug #22429
+
+class School(models.Model):
+    pass
+
+
+class Student(models.Model):
+    school = models.ForeignKey(School)
+
+
+class Classroom(models.Model):
+    school = models.ForeignKey(School)
+    students = models.ManyToManyField(Student, related_name='classroom')
diff --git a/tests/queries/tests.py b/tests/queries/tests.py
index 6d8996c1d8..ad6cbd910c 100644
--- a/tests/queries/tests.py
+++ b/tests/queries/tests.py
@@ -28,7 +28,7 @@ from .models import (
     BaseA, FK1, Identifier, Program, Channel, Page, Paragraph, Chapter, Book,
     MyObject, Order, OrderItem, SharedConnection, Task, Staff, StaffUser,
     CategoryRelationship, Ticket21203Parent, Ticket21203Child, Person,
-    Company, Employment, CustomPk, CustomPkTag)
+    Company, Employment, CustomPk, CustomPkTag, Classroom, School, Student)
 
 
 class BaseQuerysetTest(TestCase):
@@ -3345,3 +3345,18 @@ class ReverseM2MCustomPkTests(TestCase):
         self.assertQuerysetEqual(
             CustomPkTag.objects.filter(custom_pk=cp1), [cpt1],
             lambda x: x)
+
+
+class Ticket22429Tests(TestCase):
+    def test_ticket_22429(self):
+        sc1 = School.objects.create()
+        st1 = Student.objects.create(school=sc1)
+
+        sc2 = School.objects.create()
+        st2 = Student.objects.create(school=sc2)
+
+        cr = Classroom.objects.create(school=sc1)
+        cr.students.add(st1)
+
+        queryset = Student.objects.filter(~Q(classroom__school=F('school')))
+        self.assertQuerysetEqual(queryset, [st2], lambda x: x)