Machine learning (ML) approaches are increasingly being used to accelerate combinatorial optimization (CO) problems. We investigate the Set Cover Problem (SCP) and propose Graph-SCP, a graph neural network method that augments existing optimization solvers by learning to identify a smaller sub-problem that contains the solution space. Graph-SCP uses both supervised learning from prior solved instances and unsupervised learning to minimize the SCP objective. We evaluate the performance of Graph-SCP on synthetically weighted and unweighted SCP instances with diverse problem characteristics and complexities, and on instances from the OR Library, a canonical benchmark for SCP. We show that Graph-SCP reduces the problem size by 60–80% and achieves runtime speedups of up to 10x on average when compared to Gurobi (a state-of-the-art commercial solver), while maintaining solution quality. This is in contrast to fast greedy solutions that significantly compromise solution quality to achieve guaranteed polynomial runtime. We showcase Graph-SCP’s ability to generalize to larger problem sizes, training on SCP instances with up to 3,000 subsets and testing on SCP instances with up to 10,000 subsets.