From 1974 to 1976, Lightman was a postdoctoral fellow in astrophysics at Cornell. During this period, he began publishing poetry in small literary magazines. He was an assistant professor of astronomy at Harvard from 1976 to 1979 and from 1979 to 1989 a research scientist at the Harvard-Smithsonian Center for Astrophysics.
In 1989, Lightman was appointed professor of science and writing, and senior lecturer in physics, at the Massachusetts Institute of Technology. From 1991 to 1997, he headed the Program in Writing and Humanistic Studies at MIT. During this period, he helped create a new Communication Requirement at MIT (first instituted in 2001), which requires all MIT undergraduates to have a course equivalent in writing or speaking each of their four years. In 1995, he was appointed John E. Burchard professor of humanities at MIT, a chair named after the first dean of humanities at MIT (1948 - 1964). In 2001, Lightman co-founded the Graduate Program in Science Writing at MIT, which accepted its first students in the fall of 2002. In the same year, he resigned his chair to allow more time for his writing and became adjunct professor at MIT.
As both a distinguished physicist and an accomplished novelist, Lightman is one of only a small number of people who straddle the sciences and the humanities. He was the first professor at MIT to receive a joint appointment in the sciences and the humanities. His essay "In the Name of Love?" was the first article about love and language published in Nature, the prestigious international science journal (October 8, 2001), and his "The First Law of Thermodynamics" was the first short story published in the physics journal Physics Today (May 2005). He has lectured at more than 100 universities nationwide about the similarities and differences in the ways that scientists and artists view the world.