He played in Major League Baseball (MLB) for the Colorado Rockies, Chicago White Sox, San Francisco Giants, Los Angeles Dodgers, Atlanta Braves, New York Mets and Cleveland Indians.

The next two years were plagued by injuries and poor hitting, but he regained his starting role at third base and made strong contributions to the team in 2013 and 2014.

While in Asheville, he batted .267 with 28 doubles, nine home runs and 46 RBI in 125 games, compiling a 15-game hitting streak at one point in the season.

Uribe played for the Single-A advanced Salem Avalanche of the Carolina League in 2000, batting .256 with 13 home runs and 65 RBI in 134 games.

He made his major league debut on April 8, pinch-hitting and striking out against Jay Witasick in an 11–3 loss to the San Diego Padres.

[13] In 2003, Uribe did not play until June 3 because of an injury suffered when he was rounding the bases during a spring training game on March 1.

[17] In 2005, Uribe spent the entire season playing shortstop after the White Sox did not re-sign José Valentín.

[1][18] In 146 games, a number that would have been higher had it not been for minor injuries, Uribe batted .252 with 121 hits, 23 doubles, 16 home runs, and 74 RBI.

[19] Uribe made two memorable defensive plays for the final two outs of the 2005 World Series, first catching a ball while crashing into the third base stands and then ranging over the middle and firing an off-balance throw on a slow grounder to beat Houston Astros outfielder Orlando Palmeiro to give the White Sox their first title in 88 years.

[1] Injuries prevented him from appearing 10 games, and he also lost some starts at shortstop to Alex Cintrón because of his low on-base percentage.

[24] He also joined Derek Jeter, Miguel Tejada, Édgar Rentería, and Michael Young as the only shortstops to top 70 RBIs in 2004, 2005, and 2006.

[1] On September 29, 2007, Uribe had a walk-off RBI single against Fernando Rodney to give the White Sox a 3–2 win over the Detroit Tigers.

[26] The White Sox acquired Orlando Cabrera to play shortstop in 2008, forcing Uribe to compete with Alexei Ramírez, Danny Richar, and Pablo Ozuna for the position in spring training.

[28][29][30] However, Uribe took over third base from Josh Fields (who had spent a week filling in for an injured Joe Crede) on August 1.

[36] On July 10, Uribe bobbled a ground ball with one out in the eighth inning of Jonathan Sánchez's no-hitter against San Diego, allowing Chase Headley to reach first base.

[37] In 122 games (398 at-bats), Uribe batted .289 (his highest average since 2001) with 115 hits, 26 doubles, 16 home runs, and 55 RBI.

[40][41] He hit a game-winning two-run home run on September 5 against Jonathan Broxton, turning a 4–3 deficit into a 5–4 victory over the Los Angeles Dodgers.

[42] On September 23, Uribe hit a grand slam against Ryan Dempster and a two-run home run in the second inning against the Cubs for a total of six RBIs, helping the Giants win 13–0.

[1] In Game 4 of the National League Championship Series against the Phillies on October 20, Uribe had a walk-off sacrifice fly against Roy Oswalt in a 6–5 victory.

[44] In Game 6, on October 23, he hit a go-ahead solo home run against Ryan Madson in the top of the eighth, which gave the Giants a 3–2 victory, sending them to the World Series.

[45] In Game 1 of the World Series on October 27, he hit a three-run home run against Darren O'Day which proved decisive in the Giants' 11–7 victory over the Texas Rangers.

[50] He was expected to return after 15 days, but the injury didn't get better and was recharacterized as a sports hernia, which needed season-ending surgery.

[1] On October 7, during Game 4 of the NLDS, Uribe hit a two-run home run in the bottom of the eighth inning to put Los Angeles ahead of the Atlanta Braves 4–3.

[1] On May 27, 2015, Uribe was traded to the Atlanta Braves (with Chris Withrow) in exchange for Alberto Callaspo, Eric Stults, Ian Thomas and Juan Jaime.

[62] The trade was finalized during the Braves' three-game series at Dodger Stadium, and Uribe appeared in his new team's uniform in the third game, going 0-for-3 in the Atlanta win.

[64] Uribe's popularity as a Dodger extended past his trade, as a scheduled bobblehead night went ahead as planned after he had left the team for the Braves.

[65] On July 24, 2015, the Braves traded Uribe and Kelly Johnson to the New York Mets for John Gant and Rob Whalen.

[72] On June 12, 2016, in Anaheim, Uribe had to be carted off the field after being hit in the crotch by a ground ball which came off the bat of Mike Trout at 106 miles per hour (171 km/h).

Despite claims by the San Cristóbal Province District Attorney that there was no firm evidence that Uribe was involved in the incident, a judge decided to press forward with the case.

Although a defense motion to bar him from leaving the country was rejected, it was ruled on January 5, 2007, that Uribe must appear before a court on the 15 and the 30 of every month until the case was resolved.