He played baseball at Keyser High School in Keyser, West Virginia, at Potomac State College, and at Allegany Community College, He began his professional career with the San Diego Padres after being drafted in 1981. He played in such outposts as Walla Walla, Reno, Beaumont, and Las Vegas, before making his debut with the Padres in 1986.

The portly outfielder was dealt to the Philadelphia Phillies during the 1989 season, and he blossomed into an All-Star as the team used him primarily at first base. Kruk played in the All-Star Game in 1991, 1992, and 1993. In 1993, he had a memorable at bat when he flailed wildly at 98 mile per hour fastballs from Seattle Mariners pitcher Randy Johnson. Johnson's initial "Mr. Snappy" pitch was so far inside and above his head that the intimidated Kruk backed up seemingly into the on-deck circle for the remainder of this plate appearance.

Kruk, who batted .316 in 1993, was also the leader of the Phillies' "Macho Row" which led the team to the World Series against the Toronto Blue Jays; in the losing effort, Kruk batted .348 in the Series.

During spring training in 1994, Kruk was diagnosed with testicular cancer after an errant pickoff throw from teammate Mitch Williams hit him in the groin and broke his protective cup. Additionally, weight gain and the astroturf at Veterans Stadium exacerbated his knee problems. After the 1994 season, Kruk was granted free agency.

Moving to the American League to serve as a designated hitter, Kruk signed with the Chicago White Sox. He was effective with the "pale hose" but he was tired of the game. On July 30, 1995, Kruk singled and took himself out of the game. He left the ballpark never to play again. He finished his 10-year career with exactly a .300 batting average and exactly 100 home runs.

A quotable character throughout his career who later wrote a book called I Ain't an Athlete, Lady published in 1994, Kruk turned to broadcasting and commenting on the game. He has since worked for FOX and local telecasts in Philadelphia. In 2004, he was hired by ESPN as an analyst on Baseball Tonight. He also writes a column called Chewing the Fat on ESPN.com.

Rather than be self-conscious about his decidedly non-athletic-looking body, Kruk would often joke about it. He once quipped that he needed two hands to haul ass.