The Florida Marlins acquired Nolasco, Sergio Mitre, and Renyel Pinto from the Cubs for Juan Pierre on December 7, 2005.

Nolasco went on to finish the 2006 season with a 4.82 ERA, 140 innings pitched, 41 walks, 99 strikeouts, a 1.41 WHIP, and an 11-11 record in 35 games.

On September 30, 2009, Nolasco struck out 16 batters, breaking A. J. Burnett's record for 14 strikeouts in a single game for the Florida Marlins.

[4] Nolasco finished the 2009 season with a 13-9 record, a 5.06 ERA, a 1.25 WHIP, and a career high 195 strikeouts in 185 innings pitched.

He missed the entire month of September after undergoing season ending surgery to repair a torn meniscus on his right knee.

Nolasco finished the 2011 season 10-12 in 33 starts with a 4.67 ERA, a 1.40 WHIP, 148 strikeouts, and 44 walks in 206 innings pitched while allowing a league leading 244 hits.

Despite an ERA below 4, Nolasco had more losses than wins during that stretch due to the fact the Marlins were dead last in the league in runs scored.

On July 6, 2013, he was traded to the Los Angeles Dodgers for Josh Wall and minor-league pitchers Steve Ames and Ángel Sánchez.

On October 15, 2013, Nolasco made his only career postseason appearance in game 4 of the NLCS against the St. Louis Cardinals but was tagged for a loss after allowing 3 runs in 4 innings.

[8] Duffey ended up being sent down to AAA before the season began, which ultimately resulted in Nolasco winning the fifth spot in the Twins starting rotation.

On August 1, 2016, the Twins traded Nolasco with Alex Meyer plus cash in exchange for Angels pitchers Hector Santiago and Alan Busenitz.

[11] Nolasco finished the 2016 season on a high note by winning 3 consecutive starts without allowing a single earned run.

[14] On February 8, 2019, Nolasco signed a minor league contract with the Arizona Diamondbacks that included an invitation to spring training.

Nolasco's older brother, Dave, attended Riverside Community College and was selected by the Milwaukee Brewers in the 23rd round of the 2001 MLB draft.