In a statement issued to the Pittsburgh Post-Gazette from their Raleigh, N.C., home, Cowher said his wife died Friday with her family at her side.
"Sadly, my wife Kaye lost her battle with cancer on Friday," the statement said. "Kaye was such a loving and compassionate person and she was the foundation of our family.
"Kaye was always at my side throughout my career as a player, coach, NFL analyst and, most importantly, as a parent to our three daughters Meagan, Lauren and Lindsay. They will miss their mother dearly."
The newspaper said the Cowhers met when they were attending North Carolina State University in 1976 when Bill Cowher was on the football team and the former Kaye Young, as well as her twin sister Faye, were members of the women's basketball squad.
Faye and Kaye later played for the Women's Professional Basketball League and appeared in Wrigley's Doublemint Gum commercials together.
All three Cowher daughters were also standout basketball players, with Meagan and Lauren Cowher playing college ball together at Princeton University, the Post-Gazette said.