diff --git a/docs/source/common_issues.rst b/docs/source/common_issues.rst
index 5d409754bb7f..1c73f7ae4347 100644
--- a/docs/source/common_issues.rst
+++ b/docs/source/common_issues.rst
@@ -382,6 +382,23 @@ More specifically, mypy will understand the use of ``sys.version_info`` and
    else:
        # Other systems
 
+As a special case, you can also use one of these checks in a top-level
+(unindented) ``assert``; this makes mypy skip the rest of the file.
+Example:
+
+.. code-block:: python
+
+   import sys
+
+   assert sys.platform != 'win32'
+
+   # The rest of this file doesn't apply to Windows.
+
+Some other expressions exhibit similar behavior; in particular,
+``typing.TYPE_CHECKING``, variables named ``MYPY``, and any variable
+whose name is passed to ``--always-true`` or ``--always-false``.
+(However, ``True`` and ``False`` are not treated specially!)
+
 .. note::
 
    Mypy currently does not support more complex checks, and does not assign
diff --git a/mypy/semanal.py b/mypy/semanal.py
index 47a797504df1..ccb3ab28e971 100644
--- a/mypy/semanal.py
+++ b/mypy/semanal.py
@@ -3805,6 +3805,10 @@ def infer_reachability_of_if_statement(s: IfStmt, options: Options) -> None:
             break
 
 
+def assert_will_always_fail(s: AssertStmt, options: Options) -> bool:
+    return infer_condition_value(s.expr, options) in (ALWAYS_FALSE, MYPY_FALSE)
+
+
 def infer_condition_value(expr: Expression, options: Options) -> int:
     """Infer whether the given condition is always true/false.
 
diff --git a/mypy/semanal_pass1.py b/mypy/semanal_pass1.py
index 92018c9a223f..b8d9eba45291 100644
--- a/mypy/semanal_pass1.py
+++ b/mypy/semanal_pass1.py
@@ -24,10 +24,12 @@
     MypyFile, SymbolTable, SymbolTableNode, Var, Block, AssignmentStmt, FuncDef, Decorator,
     ClassDef, TypeInfo, ImportFrom, Import, ImportAll, IfStmt, WhileStmt, ForStmt, WithStmt,
     TryStmt, OverloadedFuncDef, Lvalue, Context, ImportedName, LDEF, GDEF, MDEF, UNBOUND_IMPORTED,
-    MODULE_REF, implicit_module_attrs
+    MODULE_REF, implicit_module_attrs, AssertStmt,
 )
 from mypy.types import Type, UnboundType, UnionType, AnyType, TypeOfAny, NoneTyp, CallableType
-from mypy.semanal import SemanticAnalyzerPass2, infer_reachability_of_if_statement
+from mypy.semanal import (
+    SemanticAnalyzerPass2, infer_reachability_of_if_statement, assert_will_always_fail,
+)
 from mypy.semanal_shared import create_indirect_imported_name
 from mypy.options import Options
 from mypy.sametypes import is_same_type
@@ -92,8 +94,14 @@ def visit_file(self, file: MypyFile, fnam: str, mod_id: str, options: Options) -
                 v._fullname = self.sem.qualified_name(name)
                 self.sem.globals[name] = SymbolTableNode(GDEF, v)
 
-            for d in defs:
+            for i, d in enumerate(defs):
                 d.accept(self)
+                if isinstance(d, AssertStmt) and assert_will_always_fail(d, options):
+                    # We've encountered an assert that's always false,
+                    # e.g. assert sys.platform == 'lol'.  Truncate the
+                    # list of statements.  This mutates file.defs too.
+                    del defs[i + 1:]
+                    break
 
             # Add implicit definition of literals/keywords to builtins, as we
             # cannot define a variable with them explicitly.
diff --git a/test-data/unit/check-unreachable-code.test b/test-data/unit/check-unreachable-code.test
index 1a36e10db69f..144cf926001a 100644
--- a/test-data/unit/check-unreachable-code.test
+++ b/test-data/unit/check-unreachable-code.test
@@ -623,3 +623,59 @@ class Child(Parent):
         reveal_type(self)       # E: Revealed type is '__main__.Child'
         return 3
 [builtins fixtures/isinstance.pyi]
+
+[case testUnreachableAfterToplevelAssert]
+import sys
+reveal_type(0)  # E: Revealed type is 'builtins.int'
+assert sys.platform == 'lol'
+reveal_type('')  # No error here :-)
+[builtins fixtures/ops.pyi]
+
+[case testUnreachableAfterToplevelAssert2]
+import sys
+reveal_type(0)  # E: Revealed type is 'builtins.int'
+assert sys.version_info[0] == 1
+reveal_type('')  # No error here :-)
+[builtins fixtures/ops.pyi]
+
+[case testUnreachableAfterToplevelAssert3]
+reveal_type(0)  # E: Revealed type is 'builtins.int'
+MYPY = False
+assert not MYPY
+reveal_type('')  # No error here :-)
+[builtins fixtures/ops.pyi]
+
+[case testUnreachableAfterToplevelAssert4]
+# flags: --always-false NOPE
+reveal_type(0)  # E: Revealed type is 'builtins.int'
+NOPE = False
+assert NOPE
+reveal_type('')  # No error here :-)
+[builtins fixtures/ops.pyi]
+
+[case testUnreachableAfterToplevelAssertImport]
+import foo
+foo.bar()  # E: "object" has no attribute "bar"
+[file foo.py]
+import sys
+assert sys.platform == 'lol'
+def bar() -> None: pass
+[builtins fixtures/ops.pyi]
+
+[case testUnreachableAfterToplevelAssertImport2]
+# flags: --platform lol
+import foo
+foo.bar()  # No error :-)
+[file foo.py]
+import sys
+assert sys.platform == 'lol'
+def bar() -> None: pass
+[builtins fixtures/ops.pyi]
+
+[case testUnreachableAfterToplevelAssertNotInsideIf]
+import sys
+if sys.version_info[0] >= 2:
+    assert sys.platform == 'lol'
+    reveal_type('')  # E: Revealed type is 'builtins.str'
+reveal_type('')  # E: Revealed type is 'builtins.str'
+[builtins fixtures/ops.pyi]