Sele was selected by the Boston Red Sox in the first-round (#23 overall) of the 1991 Major League Baseball draft. He had a team-best 4 complete games at Winter Haven and also pitched in the Florida Instructional League. He was a co-winner of the Tony Latham Memorial Award for player with the most enthusiasm. Sele advanced quickly through the Red Sox farm system, with stops at Lynchburg and New Britain in 1992.

Sele began his third pro season with Triple-A Pawtucket and pitched a one-hit 7-inning shutout in his first Triple-A start on April 10 at Columbus and was 4-0, 1.98 in final 6 starts. He was purchased from Pawtucket on June 22, 1993.

On September 6, 1993 while pitching against the White Sox in Chicago, Sele was involved in one of baseball’s more memorable fights. After two consecutive inside pitches, George Bell charged the mound. Sele, seeming to have a plan, did not move until Bell was feet from him, about to throw a punch. At the last second, Sele ducked to his left as Bell threw the punch and the burly Mo Vaughn, having rushed to the mound from first base, ran into Bell. Bell flipped backwards, crashing to the ground as both of the benches emptied and the teams made their way to the mound [1].

In 1994, Sele finished 2nd on the Red Sox staff in starts, complete games, innings, and strikeouts and tied for 2nd in wins. He went 5-1, 2.29 in 1st 8 starts through May 18 before going 3-6, 4.79 in final 14 outings despite allowing 3 or fewer earned runs in 8 of final 14 games. His complete games came in consecutive starts, May 11 against Milwaukee and May 18 in Baltimore.

Sele was the Opening Day starter in 1995, April 26 against Minnesota, and worked 5 scoreless innings in a 9-0 victory. He made just six starts, going 3-1, 3.06 and allowing right-handed batters to hit just .194 (13-67). He experienced soreness in his right arm after start on May 23 at Seattle and was placed on the 15-day disabled list on June 2 (retroactive to May 24). He made 2 rehab starts each at Sarasota, Trenton, and Pawtucket from June 21-August 22, going 0-1, 3.60 (20.0 IP, 8 ER) but continued to experience soreness and was moved to the 60-day disabled list for the remainder of the season on August 31.

In 1996, Sele ranked fourth on the Boston staff in starts, innings, strikeouts, and wins. He was placed on the 15-day disabled list on August 16 (retroactive to August 14) with a strained muscle in his left rib cage and made one start on rehab assignment on August 26 for Pawtucket before being activated on September 1.

Sele led the Red Sox in 1997 in wins and starts while ranking third in innings and strikeouts. He was 4-1, 3.72 in his first 7 starts through May and 4-1, 3.93 in a span of 5 outings from June 12 to July 3. He held right-handed batters to a .224 average, 7th best among AL starters, and tied his then-career high with 11 strikeouts on July 12 against Toronto. He was among the league leaders in hit batters (2nd, 15), walks (10th), and runs allowed (T10th) and allowed the most baserunners per 9 innings among AL starters (14.8).

Sele was traded to the Texas Rangers with Mark Bradenburg and Bill Haselman on November 6, 1997, for Damon Buford and Jim Leyritz.

Sele tied for 4th in the AL with a career-high 19 wins in 1998, matching the 4th most in Rangers’ history. He also tied for 5th in the league with 2 shutouts, set career highs for complete games, shutouts and innings pitched and led the majors with 13 victories at home. His first 2 career complete game shutouts came in a span of 3 starts, a 3-hitter on April 9 in Chicago and a 4-hitter on April 21 against Tampa Bay, the 2 lowest-hit complete games of his big league career. He won his first 5 starts of the season, going 5-0, 2.00 (36.0 IP, 8 ER) through April 26. This streak ended with a loss in Boston on May 1, snapping an overall 6-game winning streak over 2 seasons. The streak matched his career high.

In 2003, he began his 13th pro season and second with the Angels on 15-day disabled list. Sele underwent surgery (October 18, 2002) to repair partial tear of the supraspinatus muscle and labrum in his right rotator cuff (performed by Angels Medical Director Dr. Lewis Yocum). He was placed on the disabled list March 26 due to recovery from surgery and activated May 9. Sele set a career high in ERA and career lows in starts and strikeouts (53). His seven wins equaled his fewest in his major league career (1996; based on 25-or-more starts), had more walks (58) than strikeouts for first time as professional, tied for club lead with 12 hit batters (Ramón Ortiz), which tied for second in AL, and tied Angels’ season high six hits allowed in an inning, September 2 at Minnesota. He had nine runs allowed in the same game equaling his career high (May 16, 1999, vs. Baltimore; 2.1 IP), pitched into the seventh inning in one of 25 starts, won season-best three straight decisions, June 29-July 10, lost three straight decisions twice, and his longest outing was seven innings pitched, June 7 at Florida (9-2 win).

He made 21 starts in 2005 for Seattle and went 6-12 with a 5.66 ERA in 21 starts. He won back-to-back starts on May 22 and 28, allowing one earned run in 15.2 innings. He was signed to a minor league contract with Texas on August 6 and made two starts for Triple-A Oklahoma, going 1-1.

On January 25, 2007, Sele signed a minor league contract with the New York Mets, and received a non-roster invitation to spring training. On March 29, 2007, the Mets purchased Sele’s contract and placed him the 25-man roster. Sele served as the long man from the bullpen for the team.

On October 31, 2008, the Los Angeles Dodgers named Sele their minor league pitching instructor for the 2009 season. In 2012 the Dodgers named him as a Special Assistant, Player Personnel. After the 2017 season, he left the Dodgers organization to become a special assignment scout for the Miami Marlins.

Sele received only one vote in the 2013 Baseball Hall of Fame voting and will no longer appear on the ballot.