Nolasco was chosen in the fourth round of the 2001 amateur draft by the Chicago Cubs out of Rialto High School, in Rialto, California. After going a combined 42-17 in five seasons of minor league ball for the Cubs organization, he was traded to the Marlins along with Sergio Mitre and Renyel Pinto for Juan Pierre in the 2005 offseason.
Nolasco joined the Marlins rotation in mid-May of 2006, having pitched in relief after making the club out of spring training. He went 11-11 that season with a 4.82 RBI.
2007 saw Nolasco spend most of the season on the DL with a right elbow problem, pitching only 21.1 innings to go with his 1-2 record on the season.
2008 was Nolasco's best season to date. His 15 wins were a career best, as well as his 212.1 innings pitched, his 3.52 ERA and his NL second best 1.102 WHIP. He also ranked in the NL top ten with 186 strikeouts.
Nolasco enjoyed another solid season in 2009, striking out an NL seventh best 195 while compiling a 13-9 record and a 5.06 ERA.
In six Florida seasons, Nolasco has started 148 games, going 64-51 with a 4.50 ERA and 7.7 strikeouts per nine innings. His 786 strikeouts are number one on the All-Time Marlins list. He is currently signed through 2013.