After spending the latter half of 2004 and most of 2005 shuffling between Baltimore and Triple-A Ottawa, Maine recorded his first Major League win on August 13, 2005, at Camden Yards with a 1–0 shutout victory over the Toronto Blue Jays in which he started and pitched five innings.

Maine was traded to the Mets on January 21, 2006, along with right-handed reliever Jorge Julio in exchange for starting pitcher Kris Benson.

He was called up from Triple A Norfolk in early May 2006 after rookie Brian Bannister was put on the disabled list with a hamstring injury.

With Orlando Hernandez originally slated to start against the Houston Astros, early rain caused the Mets to put in Maine instead.

After his second scoreless outing, Mets manager Willie Randolph designated Maine as the rotation's fifth starter over higher-ranking prospect Mike Pelfrey.

Against Washington on August 12, Maine retired 11 of the first 12 batters he faced before Nick Johnson hit a solo home run.

Overall, Maine went 6–5 with a 3.60 earned run average in 15 starts in his debut season for the Mets, showing flashes of dominance, such as his scoreless innings streak.

However, after injuries sidelined both Pedro Martínez and Orlando Hernández, Maine found himself starting Game 1 of the National League Division Series for the Mets.

At the All-Star break, Maine led Mets starters with a 2.71 ERA, 93 strikeouts and was tied with Brad Penny for the most wins in the NL at 10 each.

On July 24, 2007, in the bottom of the 4th inning against the Pittsburgh Pirates, Maine hit a 2-run home run to left field and received a curtain call.

As late as September 18, his 7.89 strikeouts per 9 innings pitched put him the top 10 among all qualified National League starting pitchers.

On September 29, 2007, Maine threw 7.2 scoreless innings allowing 1 hit, and striking out 14 Florida Marlins, leading the Mets to a 13–0 rout.

[13] On February 17, 2011, Maine signed a minor league contract with the Colorado Rockies, including an invitation to Spring Training.

[14] On June 22, after pitching 45 innings with the Triple-A Colorado Springs Sky Sox, recording a 7.43 ERA, 35 strikeouts, and 37 walks, Maine left the team and was reportedly considering retiring from baseball.

[16] Maine was signed to the Scranton-Wilkes Barre Yankees roster on June 12[17] and made his first appearance in regular season game play in nearly a year that evening.

Throwing 65 pitches (37 for strikes) in three innings of work, he struck out four, walked two, and gave up three runs (two earned) while recording a win for the Yankees.

On December 13, 2012, Maine signed a minor league contract with the Miami Marlins that contained an invitation to spring training.

[20] On August 25, 2014, the Charlotte 49ers baseball team announced that Maine would join the staff of his alma mater as a volunteer assistant.