Easy operation, readily accessible starting materials, and short syntheses of the privileged scaffold indeno[1,2c]isoquinolinone were achieved by an multicomponent reaction (MCR)-based protocol via an ammonia−Ugi-four component reaction (4CR)/copper-catalyzed annulation sequence. The optimization and scope and limitations of this short and general sequence are described. The methodology allows an efficient construction of a wide variety of indenoisoquinolinones in just two steps.