Rondón signed with the Detroit Tigers organization as an international free agent on September 12, 2007. He first played with the organization in 2008 as a member of the Venezuelan Summer League Tigers (VSL). He started 13 games, compiling a 2–6 win–loss record and a 3.58 earned run average (ERA). In 2009, Rondón appeared in six games, starting the year with the Gulf Coast League Tigers (GCL). He made three starts, registering an 0–1 record and a 4.76 ERA. On July 10, he rejoined the VSL Tigers and made three relief appearances, posting an ERA of 13.50.

Rondón split the 2010 season between the GCL Tigers and the Lakeland Flying Tigers of the Class A-Advanced Florida State League (FSL), appearing in a combined total of 28 games, all of them as a reliever. He made 24 appearances in the GCL, leading the league with 15 saves. Rondón ended the season in the GCL with 20 consecutive scoreless outings and during that stretch, which covered 21⁄3 innings, he struck out 23 opponents. GCL hitters had a .133 batting average against Rondón, the best mark for all GCL relief pitchers in 2010. He was named a GCL all–star in 2010. Rondón finished the minor league season with four appearances for Lakeland, after he joined the Flying Tigers on August 24. Rondón spent all of 2011 with the West Michigan Whitecaps of the Class A Midwest League, appearing in 41 games before trouble with his right shoulder ended his season in August. He gathered 19 saves and posted a 2.03 ERA with the Whitecaps, and was named to appear in the 2011 Midwest League All-Star game Late in the year, Baseball America ranked Rondón as Detroit’s 12th-highest prospect. The previous year, he had been rated 13th.

Rondón started the 2012 season on Lakeland’s roster, but he was promoted to the Erie SeaWolves of the Class AA Eastern League on June 20 and then to the Toledo Mud Hens of the Class AAA International League on August 7. Between the three teams, Rondón saved 29 games and posted an ERA of 1.53 while striking out 66 opponents. His save total was the third-highest for a minor leaguer. He was named to appear in the 2012 All-Star Futures Game. He retired two hitters on four fastballs, with one fastball registering 102 miles per hour (164 km/h) on the Kaufman Stadium radar gun.

Tigers general manager Dave Dombrowski referred to Rondón as a “rare talent” after the 2012 season, and indicated that he could become the Tigers closer in 2013. Rondón struggled early in spring training, but began to improve with mechanical changes. The Tigers optioned Rondón to Toledo for the start of the 2013 season. They promoted him to the major leagues on April 23, but did not use him as their closer. He made his Major League debut on April 25, 2013 against the Kansas City Royals. He entered the game in relief in the eighth inning. His first batter faced was Billy Butler, who singled to right field. His pitching line for this first inning was two hits, one run scored.

Bruce returned to Toledo in early May, where he posted 14 saves and a 1.52 ERA, with 40 strikeouts and 13 walks in 29⁄3 innings. The Tigers recalled him to the major league club on June 28, 2013. He earned his first major league save on August 30, 2013 against the Cleveland Indians. He posted a 3.45 ERA in his first major league season, striking out 30 batters in 28⁄3 innings.

Expected to be one of the Tigers’ primary setup men for 2014, Rondón underwent Tommy John surgery to repair a torn ligament in his right elbow during spring training. After the procedure, Rondón missed the entire 2014 season. He returned to pitch for the Tigers midway through the 2015 season. On September 22, 2015, Rondón was sent home by the Tigers due to their displeasure with his effort level. In 35 appearances this season, he posted a 1–0 record, with five saves in nine opportunities, a 5.81 ERA, a 1.61 WHIP, and 36 strikeouts. In 31 innings, he allowed 31 hits and 19 walks, while issuing a team-high 5.5 walks per nine innings.

Preparing for the 2016 season, Rondón lost 15 pounds (6.8 kg) and made mechanical changes to his delivery. The Tigers optioned Rondón to the Mud Hens on March 28, 2016. Rondón was recalled to the Tigers on June 19, 2016, and he pitched two scoreless innings of relief against the Kansas City Royals. Rondón made 37 relief appearances in the 2016 season, compiling a 5–2 record with a 2.97 ERA and 45 strikeouts in 36 ⁄3 innings.

On January 13, 2017, the Tigers avoided arbitration with Rondón, agreeing on a one-year, $850,000 contract. He appeared in the 2017 World Baseball Classic for the Venezuelan national baseball team. During the 2017 season, Rondón pitched 15 ⁄3, allowing 19 runs on 21 hits, before he was demoted to Toledo. The Tigers did not include Rondón in their September call-ups. He was non-tendered and became a free agent on December 1, 2017. His major league career with the Tigers ended with a 5.00 ERA and seven saves in 123 relief appearances.

On February 1, 2018, Rondón signed a minor league contract with the Chicago White Sox. He had his contract purchased on April 8, 2018. He entered the game that same day against the Tigers striking out all four batters he faced. He was designated for assignment on July 12 after posting an ERA of 8.49 in 29 ⁄3 innings. He elected free agency on July 17, 2018.

On April 20, 2020, Rondón signed with the Rieleros de Aguascalientes of the Mexican League.