Wisoff graduated from Norfolk Academy, Norfolk, Virginia, in 1976, received a bachelor of science degree in physics (with Highest Distinction) from University of Virginia in 1980, a master of science degree and a doctorate in applied physics from Stanford University in 1982 and 1986 respectively.

Selected by NASA in January 1990, Wisoff became an astronaut in July 1991. He is qualified for flight assignment as a mission specialist. His technical assignments to date include: spacecraft communicator (CAPCOM) in Mission Control; flight software verification in the Shuttle Avionics Integration Laboratory (SAIL); coordinating flight crew equipment; evaluating extravehicular activity (EVA) equipment and techniques for the construction of Space Station; lead for the Payloads and Habitability Branch of the Astronaut Office. A veteran of four space flights, STS-57 in 1993, STS-68 in 1994, STS-81 in 1997 and STS-92 in 2000, Wisoff has logged a total of 42 days, 56 hours, 1 minute and 48 seconds in space, including 19 hours and 53 minutes of EVA time in three space walks.

Wisoff’s graduate work at Stanford University (as a National Science Foundation Graduate Fellow) focused on development of short wavelength lasers. Wisoff later joined the faculty of the Electrical and Computer Engineering Department at Rice University. His research focused on the development of new vacuum ultraviolet and high intensity laser sources. He also collaborated with researchers from regional Texas Medical Centers on the applications of lasers to the reconstruction of damaged nerves and has collaborated with researchers at Rice University on new techniques for growing and evaluating semiconductor materials using lasers. Wisoff has contributed numerous papers at technical conferences and in journals in the areas of lasers and laser applications. On October 1, 2013, Wisoff was named the interim principal associate director for the NIF and Photon Sciences directorate at Lawrence Livermore National Laboratory in place of the outgoing Ed Moses.