diff --git a/src/compiler/checker.ts b/src/compiler/checker.ts
index 3de21bebf7681..b5d42632d7fad 100644
--- a/src/compiler/checker.ts
+++ b/src/compiler/checker.ts
@@ -14662,7 +14662,10 @@ namespace ts {
                         // types rules (i.e. proper contravariance) for inferences.
                         inferTypes(context.inferences, checkType, extendsType, InferencePriority.NoConstraints | InferencePriority.AlwaysStrict);
                     }
-                    combinedMapper = mergeTypeMappers(mapper, context.mapper);
+                    // It's possible for 'infer T' type paramteters to be given uninstantiated constraints when the
+                    // those type parameters are used in type references (see getInferredTypeParameterConstraint). For
+                    // that reason we need context.mapper to be first in the combined mapper. See #42636 for examples.
+                    combinedMapper = mapper ? combineTypeMappers(context.mapper, mapper) : context.mapper;
                 }
                 // Instantiate the extends type including inferences for 'infer T' type parameters
                 const inferredExtendsType = combinedMapper ? instantiateType(unwrapNondistributiveConditionalTuple(root, root.extendsType), combinedMapper) : extendsType;
diff --git a/tests/baselines/reference/inferTypeParameterConstraints.js b/tests/baselines/reference/inferTypeParameterConstraints.js
new file mode 100644
index 0000000000000..2d367bef27c36
--- /dev/null
+++ b/tests/baselines/reference/inferTypeParameterConstraints.js
@@ -0,0 +1,23 @@
+//// [inferTypeParameterConstraints.ts]
+// Repro from #42636
+
+type SubGuard<A, X extends [A]> = X;
+
+type IsSub<M extends any[], S extends any[]> = M extends [...SubGuard<M[number], infer B>, ...S, ...any[]] ? B : never;
+
+type E0 = IsSub<[1, 2, 3, 4], [2, 3, 4]>;  // [1 | 2 | 3 | 4]
+
+type E1 = [1, 2, 3, 4] extends [...infer B, 2, 3, 4, ...any[]] ? B : never;  // unknown[]
+
+// Repro from #42636
+
+type Constrain<T extends C, C> = unknown;
+
+type Foo<A> = A extends Constrain<infer X, A> ? X : never;
+
+type T0 = Foo<string>;  // string
+
+
+//// [inferTypeParameterConstraints.js]
+"use strict";
+// Repro from #42636
diff --git a/tests/baselines/reference/inferTypeParameterConstraints.symbols b/tests/baselines/reference/inferTypeParameterConstraints.symbols
new file mode 100644
index 0000000000000..2c96c9e53bed1
--- /dev/null
+++ b/tests/baselines/reference/inferTypeParameterConstraints.symbols
@@ -0,0 +1,51 @@
+=== tests/cases/compiler/inferTypeParameterConstraints.ts ===
+// Repro from #42636
+
+type SubGuard<A, X extends [A]> = X;
+>SubGuard : Symbol(SubGuard, Decl(inferTypeParameterConstraints.ts, 0, 0))
+>A : Symbol(A, Decl(inferTypeParameterConstraints.ts, 2, 14))
+>X : Symbol(X, Decl(inferTypeParameterConstraints.ts, 2, 16))
+>A : Symbol(A, Decl(inferTypeParameterConstraints.ts, 2, 14))
+>X : Symbol(X, Decl(inferTypeParameterConstraints.ts, 2, 16))
+
+type IsSub<M extends any[], S extends any[]> = M extends [...SubGuard<M[number], infer B>, ...S, ...any[]] ? B : never;
+>IsSub : Symbol(IsSub, Decl(inferTypeParameterConstraints.ts, 2, 36))
+>M : Symbol(M, Decl(inferTypeParameterConstraints.ts, 4, 11))
+>S : Symbol(S, Decl(inferTypeParameterConstraints.ts, 4, 27))
+>M : Symbol(M, Decl(inferTypeParameterConstraints.ts, 4, 11))
+>SubGuard : Symbol(SubGuard, Decl(inferTypeParameterConstraints.ts, 0, 0))
+>M : Symbol(M, Decl(inferTypeParameterConstraints.ts, 4, 11))
+>B : Symbol(B, Decl(inferTypeParameterConstraints.ts, 4, 86))
+>S : Symbol(S, Decl(inferTypeParameterConstraints.ts, 4, 27))
+>B : Symbol(B, Decl(inferTypeParameterConstraints.ts, 4, 86))
+
+type E0 = IsSub<[1, 2, 3, 4], [2, 3, 4]>;  // [1 | 2 | 3 | 4]
+>E0 : Symbol(E0, Decl(inferTypeParameterConstraints.ts, 4, 119))
+>IsSub : Symbol(IsSub, Decl(inferTypeParameterConstraints.ts, 2, 36))
+
+type E1 = [1, 2, 3, 4] extends [...infer B, 2, 3, 4, ...any[]] ? B : never;  // unknown[]
+>E1 : Symbol(E1, Decl(inferTypeParameterConstraints.ts, 6, 41))
+>B : Symbol(B, Decl(inferTypeParameterConstraints.ts, 8, 40))
+>B : Symbol(B, Decl(inferTypeParameterConstraints.ts, 8, 40))
+
+// Repro from #42636
+
+type Constrain<T extends C, C> = unknown;
+>Constrain : Symbol(Constrain, Decl(inferTypeParameterConstraints.ts, 8, 75))
+>T : Symbol(T, Decl(inferTypeParameterConstraints.ts, 12, 15))
+>C : Symbol(C, Decl(inferTypeParameterConstraints.ts, 12, 27))
+>C : Symbol(C, Decl(inferTypeParameterConstraints.ts, 12, 27))
+
+type Foo<A> = A extends Constrain<infer X, A> ? X : never;
+>Foo : Symbol(Foo, Decl(inferTypeParameterConstraints.ts, 12, 41))
+>A : Symbol(A, Decl(inferTypeParameterConstraints.ts, 14, 9))
+>A : Symbol(A, Decl(inferTypeParameterConstraints.ts, 14, 9))
+>Constrain : Symbol(Constrain, Decl(inferTypeParameterConstraints.ts, 8, 75))
+>X : Symbol(X, Decl(inferTypeParameterConstraints.ts, 14, 39))
+>A : Symbol(A, Decl(inferTypeParameterConstraints.ts, 14, 9))
+>X : Symbol(X, Decl(inferTypeParameterConstraints.ts, 14, 39))
+
+type T0 = Foo<string>;  // string
+>T0 : Symbol(T0, Decl(inferTypeParameterConstraints.ts, 14, 58))
+>Foo : Symbol(Foo, Decl(inferTypeParameterConstraints.ts, 12, 41))
+
diff --git a/tests/baselines/reference/inferTypeParameterConstraints.types b/tests/baselines/reference/inferTypeParameterConstraints.types
new file mode 100644
index 0000000000000..207119f0cd2b2
--- /dev/null
+++ b/tests/baselines/reference/inferTypeParameterConstraints.types
@@ -0,0 +1,26 @@
+=== tests/cases/compiler/inferTypeParameterConstraints.ts ===
+// Repro from #42636
+
+type SubGuard<A, X extends [A]> = X;
+>SubGuard : X
+
+type IsSub<M extends any[], S extends any[]> = M extends [...SubGuard<M[number], infer B>, ...S, ...any[]] ? B : never;
+>IsSub : IsSub<M, S>
+
+type E0 = IsSub<[1, 2, 3, 4], [2, 3, 4]>;  // [1 | 2 | 3 | 4]
+>E0 : [1 | 4 | 2 | 3]
+
+type E1 = [1, 2, 3, 4] extends [...infer B, 2, 3, 4, ...any[]] ? B : never;  // unknown[]
+>E1 : unknown[]
+
+// Repro from #42636
+
+type Constrain<T extends C, C> = unknown;
+>Constrain : unknown
+
+type Foo<A> = A extends Constrain<infer X, A> ? X : never;
+>Foo : Foo<A>
+
+type T0 = Foo<string>;  // string
+>T0 : string
+
diff --git a/tests/cases/compiler/inferTypeParameterConstraints.ts b/tests/cases/compiler/inferTypeParameterConstraints.ts
new file mode 100644
index 0000000000000..4a1a6dcdbdb84
--- /dev/null
+++ b/tests/cases/compiler/inferTypeParameterConstraints.ts
@@ -0,0 +1,19 @@
+// @strict: true
+
+// Repro from #42636
+
+type SubGuard<A, X extends [A]> = X;
+
+type IsSub<M extends any[], S extends any[]> = M extends [...SubGuard<M[number], infer B>, ...S, ...any[]] ? B : never;
+
+type E0 = IsSub<[1, 2, 3, 4], [2, 3, 4]>;  // [1 | 2 | 3 | 4]
+
+type E1 = [1, 2, 3, 4] extends [...infer B, 2, 3, 4, ...any[]] ? B : never;  // unknown[]
+
+// Repro from #42636
+
+type Constrain<T extends C, C> = unknown;
+
+type Foo<A> = A extends Constrain<infer X, A> ? X : never;
+
+type T0 = Foo<string>;  // string