John Mellor-Crummey's  research focuses on software technology for high performance parallel computing. His current research includes tools for measurement and analysis of application performance, tools for dynamic data race detection, and techniques for network performance analysis and optimization. He leads the research and development of the HPCToolkit Performance Tools, principally supported by the Exascale Computing Project. His past work has included development of data parallel compilers, runtime systems for scalable parallel computing, scalable software synchronization algorithms for shared-memory multiprocessors, and techniques for execution replay of parallel programs.

In 2006, John Mellor-Crummey and Michael L. Scott were awarded the Dijkstra Prize in Distributed Computing for their paper Algorithms for Scalable Synchronization on Shared-Memory Multiprocessors, ACM Transactions on Computer Systems, February, 1991. In 2013, John Mellor-Crummey was named an ACM Fellow for contributions to parallel and high performance computing.