Karros was selected by the Los Angeles Dodgers in the sixth round of the 1988 Major League Baseball draft. He made his Major League debut as a pinch runner on September 1, 1991, against the Chicago Cubs. He made his first start, at first base, on September 4, 1991, against the St. Louis Cardinals, when he was 0-for-3 with two strikeouts. Karros recorded his first Major League hit as a pinch hitter in the bottom of the 12th inning against Cincinnati Reds pitcher Milt Hill on September 16, 1991. It was a two-run RBI double to left field, his only hit in 14 batting appearances during the 1991 season.
In his first at-bat of the 1992 season, on April 9 against the San Diego Padres, Karros hit a two-run shot to deep left field off Craig Lefferts for his first career home run. He became a full-time starter for the Dodgers that season, appearing in 149 games and hitting 20 home runs while driving in 88 runs. He was named the 1992 National League Rookie of the Year. Karros put up consistent numbers throughout his career with the Dodgers, with a batting average of just under .270 and an average of almost 25 home runs a year.
He became the third Dodgers player in history to record 30 home runs and 100 RBI in five different seasons (alongside Duke Snider and Gil Hodges). Karros also remains the only player in Dodgers history to hit two homers in the same inning, accomplishing the feat on August 22, 2000. 1999 was his best statistical year with the Dodgers when he hit .304 with 34 home runs and 112 RBI. His career 270 home runs as a Los Angeles Dodger are the most since the team moved to Los Angeles, and third in all-time Dodgers history.
On December 2, 2002, he was traded along with Mark Grudzielanek to the Chicago Cubs in exchange for Todd Hundley and Chad Hermansen. Karros started the season as the Cubs’ backup first baseman but took over the role at the beginning of June after Hee-seop Choi was injured in a collision with Cubs teammate Kerry Wood. After playing the 2003 season with the Cubs he was granted free agency from the team at the end of the year. In 114 games with the Cubs, he hit .286 with 12 home runs and 40 RBI.
