He worked at Swarthmore College from 1962 to 1966, first as an instructor and then as an assistant professor. He then worked as an assistant professor at Princeton University until 1968. Since 1968, he has been at the University of Michigan, where he is now a Distinguished University Professor Emeritus.
He specializes in the philosophy of physics, approaching a wide range of issues from a position best described as highly skeptical of many of the metaphysical conclusions commonly drawn in the physical sciences. He advocates the 'MIMO' (metaphysics in, metaphysics out) principle, claiming that much of the metaphysical content of interpreted theories in the special sciences arises from metaphysical assumptions made during their formulation.
While at Swarthmore, Sklar met and married Swarthmore undergraduate Elizabeth Sherr Sklar, who would later become an English professor at Wayne State University. Their daughter is mathematician Jessica Sklar.