During his career, he played in Major League Baseball (MLB) for the Seattle Mariners, Boston Red Sox, Los Angeles Dodgers, Atlanta Braves, Cleveland Indians, New York Yankees, and Texas Rangers.

Lowe attended Edsel Ford High School in Dearborn, Michigan, where he was a four-sport letterman in baseball, golf, soccer, and basketball.

Lowe made his major league debut on April 26, 1997, working 3+2⁄3 innings in relief against the Toronto Blue Jays.

His first career win came on June 6 against the Detroit Tigers, pitching 5+1⁄3 innings and giving up 3 runs in the Mariners' 6–3 victory.

[2] Seattle, however, was desperate for immediate bullpen help,[3] and packaged Lowe and catcher Jason Varitek into a deal with the Boston Red Sox for Heathcliff Slocumb.

[4][5][1][6] The trade on July 31 by Mariners' vice president Woody Woodward is considered one of the most lopsided in MLB history.

[1] Despite recording 24 saves early in the 2001 season, Lowe lost the closer's job soon after the trading deadline when the Red Sox acquired Ugueth Urbina.

He recorded an improbable save in deciding Game 5 of the 2003 American League Division Series, helped by two clutch strikeouts.

After giving up a leadoff single to the Cubs' Jerry Hairston Jr., Lowe did not allow another Chicago hit, picking up a one-hit, two-walk, 7–0 complete game victory while facing only 29 batters.

Lowe was chosen by manager Joe Torre to start Game 1 of the National League Championship series against the Philadelphia Phillies on October 9, 2008.

[citation needed] Lowe beat the Phillies 4–1 on Opening Night, going 8 innings and giving up just 2 hits and 0 runs.

[15] Following the 2011 season, the Braves traded Lowe to the Cleveland Indians for minor league left-handed relief pitcher Chris Jones.

[34] Lowe was diagnosed with attention deficit disorder and received permission to treat it with Adderall, a substance normally banned by Major League Baseball, but with exceptions allowed on a case-by-case basis.

[35] Lowe was charged with fourth-degree domestic violence by King County police in 1997 after his girlfriend claimed that he struck her.

Lowe was released on $1,000 bond the next day, whereupon he allegedly violated a no-contact order by returning to her home shortly thereafter.

The trooper who stopped him detected an odor of alcohol and administered a field sobriety test, which resulted in Lowe's arrest.

[41] Lowe finished second to Mark Mulder in the July 2017 American Century Championships celebrity golf tournament.