He was signed by the New York Mets as an undrafted free agent following an open tryout at Grossmont College.

[8] In Amazin', Peter Golenbock's oral history of the New York Mets, Hall of Fame catcher Gary Carter said he gave Mitchell the nickname "World" for his ability to play in the infield and outfield.

[11] After spending the 1985 season in the minor leagues, Mitchell returned to the Mets in 1986, batting .277 with 12 home runs and 43 RBI in 108 games.

He would eventually score the tying run on Bob Stanley's wild pitch to Mookie Wilson.

The interviewer then commented that maybe the increased mobility helped Mitchell to make the famous 1989 barehanded catch of Ozzie Smith's fly ball.

[11][16] On July 4, 1987, Mitchell was traded to the San Francisco Giants as part of a multi-player trade that also sent pitchers Dave Dravecky and Craig Lefferts to San Francisco in exchange for third baseman Chris Brown and pitchers Keith Comstock, Mark Davis, and Mark Grant.

[17] While Dravecky was initially considered to be the key to the trade for the Giants, it was Mitchell who emerged as a star player.

In that season, he batted .291 with a league-best 47 home runs and 125 RBI in 154 games, leading the team to the playoffs and winning the National League's Most Valuable Player award, the first by a Giant since Willie McCovey in 1969.

[11] In the 1989 postseason, Mitchell posted a .353 average, two home runs and 7 RBI in the NLCS, helping the Giants to their first World Series appearance since 1962.

[11][20] Mitchell set the tone for his charmed 1989 season early in the year with a unique defensive play on April 26.

[21][22] Mitchell made another All-Star team in 1990, and finished the season batting .290 with 35 home runs and 93 RBI in 140 games.

[24] Mitchell arrived at spring training 30 pounds (14 kg) overweight, and struggled to begin the season, batting just .222 with two home runs and 20 RBI through the end of May.

Because of the baseball strike, he opted to play for the Fukuoka Daiei Hawks in Japan the following year,[27] where he became the highest-paid player in Japanese history.

[30] He hit .304 with two home runs and 13 RBI in 27 games with Boston before being traded back to the Reds in exchange for infielder Roberto Mejía and pitcher Brad Tweedlie on July 30.

[41] In the independent leagues as manager of the Sonoma County Crushers in 2000, he was suspended for nine games after punching the opposing team's owner in the mouth during a brawl.