diff --git a/src/compiler/checker.ts b/src/compiler/checker.ts
index 3ac6cc094fe7f..b5c0978d8c0a6 100644
--- a/src/compiler/checker.ts
+++ b/src/compiler/checker.ts
@@ -5949,6 +5949,7 @@ namespace ts {
                     }
                 }
 
+
                 // Synthesize declarations for a symbol - might be an Interface, a Class, a Namespace, a Type, a Variable (const, let, or var), an Alias
                 // or a merge of some number of those.
                 // An interesting challenge is ensuring that when classes merge with namespaces and interfaces, is keeping
@@ -6317,7 +6318,10 @@ namespace ts {
                     const baseTypes = getBaseTypes(classType);
                     const implementsTypes = getImplementsTypes(classType);
                     const staticType = getTypeOfSymbol(symbol);
-                    const staticBaseType = getBaseConstructorTypeOfClass(staticType as InterfaceType);
+                    const isClass = !!staticType.symbol?.valueDeclaration && isClassLike(staticType.symbol.valueDeclaration);
+                    const staticBaseType = isClass
+                        ? getBaseConstructorTypeOfClass(staticType as InterfaceType)
+                        : anyType;
                     const heritageClauses = [
                         ...!length(baseTypes) ? [] : [createHeritageClause(SyntaxKind.ExtendsKeyword, map(baseTypes, b => serializeBaseType(b, staticBaseType, localName)))],
                         ...!length(implementsTypes) ? [] : [createHeritageClause(SyntaxKind.ImplementsKeyword, map(implementsTypes, b => serializeBaseType(b, staticBaseType, localName)))]
@@ -6353,7 +6357,17 @@ namespace ts {
                     const staticMembers = flatMap(
                         filter(getPropertiesOfType(staticType), p => !(p.flags & SymbolFlags.Prototype) && p.escapedName !== "prototype" && !isNamespaceMember(p)),
                         p => serializePropertySymbolForClass(p, /*isStatic*/ true, staticBaseType));
-                    const constructors = serializeSignatures(SignatureKind.Construct, staticType, baseTypes[0], SyntaxKind.Constructor) as ConstructorDeclaration[];
+                    // When we encounter an `X.prototype.y` assignment in a JS file, we bind `X` as a class regardless as to whether
+                    // the value is ever initialized with a class or function-like value. For cases where `X` could never be
+                    // created via `new`, we will inject a `private constructor()` declaration to indicate it is not createable.
+                    const isNonConstructableClassLikeInJsFile =
+                        !isClass &&
+                        !!symbol.valueDeclaration &&
+                        isInJSFile(symbol.valueDeclaration) &&
+                        !some(getSignaturesOfType(staticType, SignatureKind.Construct));
+                    const constructors = isNonConstructableClassLikeInJsFile ?
+                        [createConstructor(/*decorators*/ undefined, createModifiersFromModifierFlags(ModifierFlags.Private), [], /*body*/ undefined)] :
+                        serializeSignatures(SignatureKind.Construct, staticType, baseTypes[0], SyntaxKind.Constructor) as ConstructorDeclaration[];
                     for (const c of constructors) {
                         // A constructor's return type and type parameters are supposed to be controlled by the enclosing class declaration
                         // `signatureToSignatureDeclarationHelper` appends them regardless, so for now we delete them here
diff --git a/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.errors.txt b/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.errors.txt
new file mode 100644
index 0000000000000..d57fb401814e6
--- /dev/null
+++ b/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.errors.txt
@@ -0,0 +1,10 @@
+tests/cases/conformance/jsdoc/declarations/index.js(4,3): error TS2339: Property 'prototype' does not exist on type '{}'.
+
+
+==== tests/cases/conformance/jsdoc/declarations/index.js (1 errors) ====
+    // https://github.com/microsoft/TypeScript/issues/35801
+    let A;
+    A = {};
+    A.prototype.b = {};
+      ~~~~~~~~~
+!!! error TS2339: Property 'prototype' does not exist on type '{}'.
\ No newline at end of file
diff --git a/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.js b/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.js
new file mode 100644
index 0000000000000..084e6f18b91c1
--- /dev/null
+++ b/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.js
@@ -0,0 +1,18 @@
+//// [index.js]
+// https://github.com/microsoft/TypeScript/issues/35801
+let A;
+A = {};
+A.prototype.b = {};
+
+//// [index.js]
+// https://github.com/microsoft/TypeScript/issues/35801
+var A;
+A = {};
+A.prototype.b = {};
+
+
+//// [index.d.ts]
+declare class A {
+    private constructor();
+    b: {};
+}
diff --git a/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.symbols b/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.symbols
new file mode 100644
index 0000000000000..6b1aa5b1fdab6
--- /dev/null
+++ b/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.symbols
@@ -0,0 +1,13 @@
+=== tests/cases/conformance/jsdoc/declarations/index.js ===
+// https://github.com/microsoft/TypeScript/issues/35801
+let A;
+>A : Symbol(A, Decl(index.js, 1, 3))
+
+A = {};
+>A : Symbol(A, Decl(index.js, 1, 3))
+
+A.prototype.b = {};
+>A.prototype : Symbol(A.b, Decl(index.js, 2, 7))
+>A : Symbol(A, Decl(index.js, 1, 3))
+>b : Symbol(A.b, Decl(index.js, 2, 7))
+
diff --git a/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.types b/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.types
new file mode 100644
index 0000000000000..ecd9ac99954a6
--- /dev/null
+++ b/tests/baselines/reference/jsDeclarationsClassLikeHeuristic.types
@@ -0,0 +1,19 @@
+=== tests/cases/conformance/jsdoc/declarations/index.js ===
+// https://github.com/microsoft/TypeScript/issues/35801
+let A;
+>A : any
+
+A = {};
+>A = {} : {}
+>A : any
+>{} : {}
+
+A.prototype.b = {};
+>A.prototype.b = {} : {}
+>A.prototype.b : any
+>A.prototype : any
+>A : {}
+>prototype : any
+>b : any
+>{} : {}
+
diff --git a/tests/cases/conformance/jsdoc/declarations/jsDeclarationsClassLikeHeuristic.ts b/tests/cases/conformance/jsdoc/declarations/jsDeclarationsClassLikeHeuristic.ts
new file mode 100644
index 0000000000000..176712b1f854a
--- /dev/null
+++ b/tests/cases/conformance/jsdoc/declarations/jsDeclarationsClassLikeHeuristic.ts
@@ -0,0 +1,10 @@
+// @allowJs: true
+// @checkJs: true
+// @target: es5
+// @outDir: ./out
+// @declaration: true
+// @filename: index.js
+// https://github.com/microsoft/TypeScript/issues/35801
+let A;
+A = {};
+A.prototype.b = {};
\ No newline at end of file