Kearns grew up in Rochester, New York where he met his future wife, Shirley Virginia Cox. He earned a degree in business administration in 1952 from the University of Rochester. Kearns entered U.S. Navy flight school and was deployed to the Mediterranean Sea aboard the USS Coral Sea as an airman. Starting in 1954, Kearns worked at IBM.

In 1971, Kearns joined Xerox Corporation as Vice President. He also served as head of U.S./Marketing and Service at Xerox in Rochester, New York and later as Vice President of Foreign Markets in Stamford, Connecticut. In 1977, he became Xerox President and Chief Operating Officer. In 1982, Kearns became CEO of Xerox Corporation. In 1985, Kearns succeeded Charles Peter McColough as Chairman of Xerox.

Kearns was nominated by President George H.W. Bush as Deputy Secretary of the U.S. Department of Education on March 22, 1991. The United States Senate confirmed him for the position on May 31, 1991.

Following the Rodney King riots in Los Angeles, California, President George H.W. Bush appointed Kearns as White House liaison to help resolve the conflict.

Kearns left the US Department of Education on January 20, 1993. He later joined the faculty of Harvard University's Graduate School of Education where he taught for two years. Kearns has served on the board of trustees for the Ford Foundation, Time Warner, Dayton Hudson, and Ryder. He is also a former Chairman of the National Urban League.

Kearns was Chairman of New American Schools, an organization dedicated to excellence in American schools. New American Schools has since merged with the American Institutes for Research.

The University of Rochester established the David T. Kearns Center for Leadership and Diversity in Science and Engineering to expand the pool of individuals who pursue undergraduate and graduate careers in the sciences and engineering.

Kearns has published three books including: Winning the Brain Race (1991), A Legacy of Learning (1999) and Crossing the Bridge: Family, Business, Education, Cancer, and the Lessons Learned (2005).

Kearns and his wife, Shirley, have four daughters and two sons. They have 18 grandchildren, one of which, Geoffrey Kearns Young is currently enrolled at the University of Alabama.