In this paper, we investigate primeness of groupoid graded rings. We provide a set of necessary and sufficient conditions for primeness of a nearly-epsilon strongly groupoid graded ring. Furthermore, we apply our main result to get a characterization of prime partial skew groupoid rings, and in particular of prime groupoid rings, thereby generalizing a classical result by Connell and partially generalizing recent results by Steinberg. © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.