A right-handed pitcher, Pavano played in Major League Baseball from 1998 to 2012 for the Montreal Expos, Florida Marlins, New York Yankees, Cleveland Indians, and Minnesota Twins.

In November 1997, the Red Sox sent Pavano to Montreal, along with pitcher Tony Armas Jr., in a trade that brought Pedro Martínez to Boston.

The Expos traded Pavano to the Florida Marlins in the middle of the 2002 season (with Graeme Lloyd, Mike Mordecai and Justin Wayne) for Cliff Floyd, Wilton Guerrero, and Claudio Vargas.

[9] Despite being plagued by injuries, Pavano became an important part of Florida's starting rotation and had a highly successful postseason in 2003 for the World Series champion Marlins.

Pavano became a free agent following the season and, despite receiving bigger offers from Boston, Detroit, and Cincinnati, chose to accept a four-year contract worth $39.95 million with the New York Yankees on December 20, 2004.

On August 15, 2006, Pavano broke two ribs in an automobile accident after he hit another vehicle with his Porsche in West Palm Beach, Florida.

Manager Joe Torre explained that the amount of work Pavano needed to do in repairing his clubhouse image was "sizable."

[19] On July 29, 2008, Pavano made his first rehab start since his Tommy John surgery for the Charleston RiverDogs, allowing one hit and one walk in two scoreless innings.

[21][22] He made his second start of the season against the Toronto Blue Jays on August 29 and was victorious, pitching six strong innings in the Yankees' 2–1 win.

[23] Since his first stint on the disabled list, Pavano did not endear himself to his Yankee teammates, and he stated that he would not visit the team when they played in Tampa Bay, near where he was rehabilitating.

[24] During a game Pavano started on September 14, he allowed three earned runs and five hits before leaving the mound in the sixth inning following a visit by the trainer and manager Joe Girardi.

"[25] Due to his repeated injuries with the Yankees, the New York media began derisively referring to Pavano as "American Idle."

[26] On August 7, 2009, Pavano was traded to the Minnesota Twins,[27] for whom he lost the clinching third game against the Yankees in the 2009 American League Division Series (ALDS).

During the stretch from May 29 to August 13, Pavano compiled a record of 11–2 with an ERA of 2.79, including twice throwing back-to-back complete games in which one was also a shutout.

[31] Pavano was the Opening Day starter for the Twins on April 1, 2011, giving up seven earned runs over 4+ innings in a 13–3 loss to the Toronto Blue Jays.

[32] On May 1, 2011, after performing poorly against the Kansas City Royals, Pavano took a bat to a trashcan in the Minnesota Twins dugout after being removed in the sixth inning of a 10–3 loss.

Francisco Liriano, Brian Duensing, Nick Blackburn, and Scott Baker all missed starts due to injuries.

[39] Pavano served as an analyst for Fox Sports Florida for Miami Marlins pre- and postgame shows starting with the 2014 season.