[6] Bruce had accepted a scholarship to play baseball at Tulane University, but opted instead to turn professional out of high school.

[8][9][10][11] Bruce's professional career began in 2005 in the Gulf Coast League, playing for the Reds' short-season rookie team.

[6] In 2006, he was promoted to the Reds' Low-A affiliate Dayton Dragons, where he excelled batting .291/.355/.516 (6th in the Midwest League) with 16 home runs (tied for 4th), 81 RBIs (4th; leading all Reds minor leaguers), and 42 doubles (leading the league), in 444 at bats,[13][6] placing him on many top prospect lists.

[2] However, during the Reds' final game of the 2007 season, Bruce was recognized for winning the Minor League Player of the Year award.

[18] On March 20, he was reassigned to the team's minor league camp, and started the season at Louisville, where he batted .364 with 10 home runs and 13 stolen bases in 49 games before he was promoted.

[17] He made his major league debut that day against right-handed pitcher Ian Snell of the Pittsburgh Pirates.

On May 31, Bruce launched his first Major League home run in the bottom of the 10th inning, to give the Reds a walk-off win.

[citation needed] On June 2, Bruce hit the third home run of his career while going 2-for-4 in Philadelphia against the Phillies' Kyle Kendrick.

In his first full week in the majors, he batted .577 (15-for-26) with three home runs, three doubles, and nine singles in addition to six bases on balls.

Following the trades of veteran outfielders Ken Griffey Jr. and Adam Dunn, Bruce hit his 12th home run of the season in a loss to the Pittsburgh Pirates.

After missing time due to injury, Bruce bounced back with back-to-back homers on April 21 and 22 against the Chicago Cubs.

[24] On July 11, Bruce fractured his right wrist while making a diving play in right field in a game against the New York Mets.

[25] On September 14, Bruce made his return against the Houston Astros, pinch hitting with the bases loaded in the seventh inning.

[6] On June 30, Bruce hit the game-winning home run off Phillies' ace Roy Halladay.

[27] On September 28, Bruce hit a bottom-of-the-ninth inning, first-pitch, walk-off home run off Astros pitcher Tim Byrdak to clinch the NL Central title for the Reds.

[22] He had 10 outfield assists (tied for 6th in the NL), and was nominated for a Rawlings Gold Glove Award for the first time in his career.

Bruce hit a go-ahead home run on April 29, giving the Reds a 6–5 win over the Houston Astros.

On June 15, Bruce hit an inside-the-park home run to ignite the Reds to a 7–3 win over the Mets.

[36] Bruce hit his 200th career home run on August 10, 2015, becoming the ninth Reds player and 319th Major Leaguer to do so.

[39] On August 1, 2016, the Reds traded Bruce to the New York Mets for Dilson Herrera and Max Wotell.

[43] For the first half of the season, he struggled offensively, hitting .212 with three home runs and 17 RBIs before being placed on the disabled list on June 19 with a right hip injury that had bothered him since mid-March.

[45] On December 3, 2018, the Mets traded Bruce, Jarred Kelenic, Anthony Swarzak, Gerson Bautista, and Justin Dunn to the Seattle Mariners for Edwin Díaz, Robinson Canó, and $20 million.

[22] On June 2, 2019, the Mariners traded Bruce and about $18.5 million to the Philadelphia Phillies for minor league third baseman Jake Scheiner.

[50] He became the fourth player to hit two home runs in his first start for the Phillies (joining Lefty O’Doul (1929), Jeremy Giambi (2002), and Daniel Nava (2017)), the first to hit two home runs including a grand slam, the first Phillies player with 10 or more total bases in his first start for the team, and the fifth player since 1920 with at least two home runs and six RBIs in his first start for an MLB team (joining Roman Mejias (1962), Brant Alyea (1970), Sam Horn (1990), and Calvin Pickering (2004)).

[50][51] Bruce became the first Phillies player since the onset of the modern era (1920) to hit four home runs in his first four games with his new team.

On February 13, 2021, Bruce signed a minor-league deal with the New York Yankees, with a $1.35 million contract option if he was named to the team.

[55] When regular first baseman Luke Voit was diagnosed with a partial meniscus tear that would keep him out of the lineup for the first few weeks of the season, the Yankees selected Bruce's contract on March 27.

[58] As Bruce's struggles became more apparent, the Yankees shifted DJ LeMahieu from second base to first, with new addition Rougned Odor filling in at second.

[59] Bruce announced his retirement from baseball on April 18, 2021, telling reporters, "Ultimately, I just felt like I couldn't perform at the level that I expected out of myself.

On December 1, 2012, in Dripping Springs, Texas, Bruce married Hannah Eastham, whom he had been dating since early in high school.