He then worked as a postdoc at the Kitt Peak National Observatory, before joining the faculty at the University of Michigan, where he rose to become Professor and Chairman of the Astronomy Department and helped to build the 2.4 meter Hiltner Telescope.

In July, 2015 he was appointed Chief Program Officer for Science at the Gordon and Betty Moore Foundation, where he is leading the team responsible for distributing more than $100 million per year for research and technology that enables fundamental scientific discoveries.

[3] At the Gordon and Betty Moore Foundation, Kirshner is an observer on the Thirty Meter International Observatory board of directors.

In 1981, along with Augustus Oemler, Jr., Paul Schechter, and Stephen Shectman, Kirshner discovered the Boötes Void in a survey of galaxy redshifts.

[4] He led work on SN 1987A, the brightest supernova since Kepler's in 1604, using the International Ultraviolet Explorer satellite in 1987 and the Hubble Space Telescope after its launch in 1990.

Brian Schmidt and Adam Riess, both of whom were among Kirshner's nineteen Ph.D students,[7] shared in the 2011 Nobel Prize in Physics for the same discovery.

[8] His account of this discovery is described in The Extravagant Universe : Exploding Stars, Dark Energy, and the Accelerating Cosmos (2002; ISBN 978-0-691-05862-7)[9] which has been translated into Japanese, Chinese, Spanish, Portuguese and Czech.

In 2014, he won the James Craig Watson Medal for service to astronomy from the National Academy of Sciences[12] and shared in the Breakthrough Prize in Fundamental Physics with the High-Z Team.