Born in Chicago, Illinois, he attended Notre Dame High School in Niles, Illinois. Luzinski spent the majority of his career with the Philadelphia Phillies (1970–1980), and retired as a member of the Chicago White Sox (1981–1984).
At 6'1' and 255 pounds, Luzinski was a well-liked member of the Phillies and a prototypical slugger. He was a career .276 hitter with 307 home runs and 1,128 RBIs. He was selected an All-Star between 1975 and 1978, being the top vote-getter for the National League in 1978. He was also MVP runner up in 1975 (when he led the National League in RBIs with 120) and 1977, when he posted career highs in batting average (.309), home runs (39) and RBIs (130).
He homered in each of the 3 National League series played from 1976 to 1978, though the Phillies did not advance to the World Series those years. In 1980, he suffered a major slump with injuries in the regular season, batting just .228 with 19 home runs and 56 RBIs, but came back with 2 game-winning hits in the 1980 National League Series, including a game-winning home run in Game 1, as Philadelphia beat Houston in five games to finally make the World Series, where they defeated the Kansas City Royals to take the title. He joined the Chicago White Sox the next season, and became one of the top designated hitters in the American League before he retired after the 1984 season.