diff --git a/crates/red_knot_python_semantic/resources/mdtest/narrow/conditionals_nested.md b/crates/red_knot_python_semantic/resources/mdtest/narrow/conditionals_nested.md
new file mode 100644
index 0000000000000..f0857fe267f17
--- /dev/null
+++ b/crates/red_knot_python_semantic/resources/mdtest/narrow/conditionals_nested.md
@@ -0,0 +1,13 @@
+# Narrowing for nested conditionals
+
+```py
+def int_instance() -> int: ...
+
+
+x = int_instance()
+
+if x != 1:
+    if x != 2:
+        if x != 3:
+            reveal_type(x)  # revealed: int & ~Literal[1] & ~Literal[2] & ~Literal[3]
+```
diff --git a/crates/red_knot_python_semantic/resources/mdtest/narrow/conditionals_not_eq.md b/crates/red_knot_python_semantic/resources/mdtest/narrow/conditionals_not_eq.md
new file mode 100644
index 0000000000000..3811d381f91e9
--- /dev/null
+++ b/crates/red_knot_python_semantic/resources/mdtest/narrow/conditionals_not_eq.md
@@ -0,0 +1,58 @@
+# Narrowing for `!=` conditionals
+
+## `x != None`
+
+```py
+x = None if flag else 1
+
+if x != None:
+    reveal_type(x)  # revealed: Literal[1]
+```
+
+## `!=` for other singleton types
+
+```py
+x = True if flag else False
+
+if x != False:
+    reveal_type(x)  # revealed: Literal[True]
+```
+
+## `x != y` where `y` is of literal type
+
+```py
+x = 1 if flag else 2
+
+if x != 1:
+    reveal_type(x)  # revealed: Literal[2]
+```
+
+## `x != y` where `y` is a single-valued type
+
+```py
+class A: ...
+
+
+class B: ...
+
+
+C = A if flag else B
+
+if C != A:
+    reveal_type(C)  # revealed: Literal[B]
+```
+
+## `!=` for non-single-valued types
+
+Only single-valued types should narrow the type:
+
+```py
+def int_instance() -> int: ...
+
+
+x = int_instance() if flag else None
+y = int_instance()
+
+if x != y:
+    reveal_type(x)  # revealed: int | None
+```
diff --git a/crates/red_knot_python_semantic/src/types.rs b/crates/red_knot_python_semantic/src/types.rs
index dd66bf173bc23..c93fc150a35b7 100644
--- a/crates/red_knot_python_semantic/src/types.rs
+++ b/crates/red_knot_python_semantic/src/types.rs
@@ -667,6 +667,55 @@ impl<'db> Type<'db> {
         }
     }
 
+    /// Return true if this type is non-empty and all inhabitants of this type compare equal.
+    pub(crate) fn is_single_valued(self, db: &'db dyn Db) -> bool {
+        match self {
+            Type::None
+            | Type::Function(..)
+            | Type::Module(..)
+            | Type::Class(..)
+            | Type::IntLiteral(..)
+            | Type::BooleanLiteral(..)
+            | Type::StringLiteral(..)
+            | Type::BytesLiteral(..) => true,
+
+            Type::Tuple(tuple) => tuple
+                .elements(db)
+                .iter()
+                .all(|elem| elem.is_single_valued(db)),
+
+            Type::Instance(class_type) => match class_type.known(db) {
+                Some(KnownClass::NoneType) => true,
+                Some(
+                    KnownClass::Bool
+                    | KnownClass::Object
+                    | KnownClass::Bytes
+                    | KnownClass::Type
+                    | KnownClass::Int
+                    | KnownClass::Float
+                    | KnownClass::Str
+                    | KnownClass::List
+                    | KnownClass::Tuple
+                    | KnownClass::Set
+                    | KnownClass::Dict
+                    | KnownClass::GenericAlias
+                    | KnownClass::ModuleType
+                    | KnownClass::FunctionType,
+                ) => false,
+                None => false,
+            },
+
+            Type::Any
+            | Type::Never
+            | Type::Unknown
+            | Type::Unbound
+            | Type::Todo
+            | Type::Union(..)
+            | Type::Intersection(..)
+            | Type::LiteralString => false,
+        }
+    }
+
     /// Resolve a member access of a type.
     ///
     /// For example, if `foo` is `Type::Instance(<Bar>)`,
@@ -1965,6 +2014,31 @@ mod tests {
         assert!(from.into_type(&db).is_singleton());
     }
 
+    #[test_case(Ty::None)]
+    #[test_case(Ty::BooleanLiteral(true))]
+    #[test_case(Ty::IntLiteral(1))]
+    #[test_case(Ty::StringLiteral("abc"))]
+    #[test_case(Ty::BytesLiteral("abc"))]
+    #[test_case(Ty::Tuple(vec![]))]
+    #[test_case(Ty::Tuple(vec![Ty::BooleanLiteral(true), Ty::IntLiteral(1)]))]
+    fn is_single_valued(from: Ty) {
+        let db = setup_db();
+
+        assert!(from.into_type(&db).is_single_valued(&db));
+    }
+
+    #[test_case(Ty::Never)]
+    #[test_case(Ty::Any)]
+    #[test_case(Ty::Union(vec![Ty::IntLiteral(1), Ty::IntLiteral(2)]))]
+    #[test_case(Ty::Tuple(vec![Ty::None, Ty::BuiltinInstance("int")]))]
+    #[test_case(Ty::BuiltinInstance("str"))]
+    #[test_case(Ty::LiteralString)]
+    fn is_not_single_valued(from: Ty) {
+        let db = setup_db();
+
+        assert!(!from.into_type(&db).is_single_valued(&db));
+    }
+
     #[test_case(Ty::Never)]
     #[test_case(Ty::IntLiteral(345))]
     #[test_case(Ty::BuiltinInstance("str"))]
diff --git a/crates/red_knot_python_semantic/src/types/narrow.rs b/crates/red_knot_python_semantic/src/types/narrow.rs
index 7d9d58995320b..23086de56b726 100644
--- a/crates/red_knot_python_semantic/src/types/narrow.rs
+++ b/crates/red_knot_python_semantic/src/types/narrow.rs
@@ -169,6 +169,14 @@ impl<'db> NarrowingConstraintsBuilder<'db> {
                     ast::CmpOp::Is => {
                         self.constraints.insert(symbol, comp_ty);
                     }
+                    ast::CmpOp::NotEq => {
+                        if comp_ty.is_single_valued(self.db) {
+                            let ty = IntersectionBuilder::new(self.db)
+                                .add_negative(comp_ty)
+                                .build();
+                            self.constraints.insert(symbol, ty);
+                        }
+                    }
                     _ => {
                         // TODO other comparison types
                     }