The goal of this paper is to study a comprehensive system called differential variational–hemivariational inequality which is composed of a nonlinear evolution equation and a time-dependent variational–hemivariational inequality in Banach spaces. Under the general functional framework, a generalized existence theorem for differential variational–hemivariational inequality is established by employing KKM principle, Minty’s technique, theory of multivalued analysis, the properties of Clarke’s subgradient. Furthermore, we explore a well-posedness result for the system, including the existence, uniqueness, and stability of the solution in mild sense. Finally, using penalty methods to the inequality, we consider a penalized problem-associated differential variational–hemivariational inequality, and examine the convergence result that the solution to the original problem can be approached, as a parameter converges to zero, by the solution of the penalized problem.