This work addresses an extension of the Aubin-Lions-Simon compactness result to generalized Bochner spaces L 2 (0, T ; H(t)), where H(t) is a family of Hilbert spaces, parameterized by t. A compactness result of this type is needed in the study of the existence of weak solutions to nonlinear evolution problems governed by partial differential equations defined on moving domains. We identify the conditions on the regularity of the domain motion in time under which our extension of the Aubin-Lions-Simon compactness result holds. Concrete examples of the application of the compactness theorem are presented, including a classical problem for the incompressible, Navier-Stokes equations defined on a given non-cylindrical domain, and a class of fluid-structure interaction problems for the incompressible, Navier-Stokes equations, coupled to the elastodynamics of a Koiter shell. The compactness result presented in this manuscript is crucial in obtaining constructive existence proofs to nonlinear, moving boundary problems, using Rothe's method. *