He played in Major League Baseball (MLB) as an outfielder and designated hitter for the Pittsburgh Pirates, Chicago White Sox, Texas Rangers and Seattle Mariners.

[5] Zisk was acquired along with Silvio Martinez by the Chicago White Sox from the Pirates for Goose Gossage and Terry Forster at the Winter Meetings on December 10, 1976.

[8] His best season was in 1977, his lone year with the White Sox, when he hit 30 home runs and had 101 RBI, both career highs, in addition to a .290 batting average in 141 games.

[5] After three seasons in Texas, Zisk was traded along with Jerry Don Gleaton, Rick Auerbach, Ken Clay, Brian Allard and minor-league right-handed pitcher Steve Finch from the Rangers to the Mariners for Willie Horton, Rick Honeycutt, Leon Roberts, Mario Mendoza and Larry Cox in an 11-player blockbuster deal on December 18, 1980.

His younger brother, John, played a season in the Texas Rangers' organization, and two for the independent Wausau Timbers of the Midwest League.