In this article, a hybrid metaheuristic method for solving the open shop scheduling problem (OSSP) is proposed. The optimization criterion is the minimization of makespan and the solution method consists of four components: a randomized initial population generation, a heuristic solution included in the initial population acquired by a Nawaz-Enscore-Ham (NEH)-based heuristic for the flow shop scheduling problem, and two interconnected metaheuristic algorithms: a variable neighborhood search and a genetic algorithm. To our knowledge, this is the first hybrid application of genetic algorithm (GA) and variable neighborhood search (VNS) for the open shop scheduling problem. Computational experiments on benchmark data sets demonstrate that the proposed hybrid metaheuristic reaches a high quality solution in short computational times. Moreover, 12 new hard, large-scale open shop benchmark instances are proposed that simulate realistic industrial cases.