A 1st round draft pick of the Toronto Blue Jays in 1990, Karsay was traded to the Athletics along with outfielder José Herrera for Rickey Henderson on July 31, 1993. A starter in his early days with the Athletics, Karsay worked mostly in middle relief and as a set-up man from 1998 on, although he also had some notable success as a closer in 2000 with the Indians and 2002 with the Yankees.
His career was marred by injuries, causing him to miss the 1995 (elbow surgery), 1996 (Tommy John surgery) and 2003 (shoulder surgery) seasons; in all, he was on the disabled list seven times.
Finally, at age 34, Karsay announced his retirement on June 18, 2006, the day after pitching two scoreless innings against the Los Angeles Dodgers and getting the win in a 17-inning marathon for the Athletics. He finished his 11-year Major League career with a 32-39 record, 41 saves, and a 4.01 ERA in 357 career appearances, including 40 starts.