De La Rosa signed with the Dodgers in 2007 and spent two seasons with their Dominican Summer League team. He was transferred to the Arizona League Dodgers in 2009 and then split 2010 between the Class-A Great Lakes Loons and Double-A Chattanooga Lookouts. Overall, he pitched in 22 games in 2010, with 13 starts and was 7–2 with a 2.37 ERA. He was selected as the Dodgers "Minor League Pitcher of the Year" and given an invite to Major League spring training for 2011. He was assigned back to Chattanooga to start the season, where he was 2–2 with a 2.92 ERA in eight starts for the Lookouts. De La Rosa was selected to the 2011 Southern League All-Star Game, but was unable to participate because he was promoted to the Dodgers. De La Rosa was called up by the Dodgers on May 24, 2011. He made his debut the same day, pitching a scoreless eighth inning against the Houston Astros, retiring the side in order, including two strikeouts. On May 27, he recorded his first career major league victory against the Florida Marlins. On June 7, 2011, De La Rosa made his first career start against the Philadelphia Phillies. He walked five of the first eleven batters he faced but settled down to allow just one run in five innings to pick up the win. He went on to pitch in 13 games for the Dodgers in 2011, including making 10 starts. His record was 4–5 with a 3.71 ERA and 60 strikeouts. In his last start of the season, on July 31 against the Arizona Diamondbacks, he suffered a tear of the ulnar collateral ligament while throwing a 94-mph fastball to Miguel Montero. He was placed on the disabled list after the game and the Dodgers announced that he would undergo Tommy John surgery and would be sidelined for up to a year. After a long recovery period and a few minor league appearances, De La Rosa finally rejoined the Dodgers on August 21, 2012. He pitched in one game for the Dodgers before being optioned back to the minors.
On October 4, 2012, the Dodgers traded De La Rosa and Jerry Sands to the Boston Red Sox to complete the August 25, 2012, trade of Carl Crawford, Josh Beckett, Adrián González, and Nick Punto and $11 million in cash for James Loney, Iván DeJesús, Jr., Allen Webster and the two players to be named later: Sands and De La Rosa. On August 3, 2013, De La Rosa was called up to the Red Sox. He made 11 appearances going 0–2 with a 5.56 ERA. On May 31, 2014, De La Rosa was called up to make a start against the Tampa Bay Rays for the injured starter Clay Buchholz. De La Rosa went seven strong innings against the Rays, giving up four hits, no runs allowed, and striking out eight batters. On June 16, 2014, De La Rosa matched his previous outing at Fenway, throwing seven innings of one-hit ball as the Red Sox beat the Twins by a score of 1–0.
Arizona Diamondbacks
On December 12, 2014, the Red Sox traded De La Rosa, Allen Webster, and Raymel Flores to the Arizona Diamondbacks in exchange for Wade Miley. After an open competition in spring training, De La Rosa won one of the opening rotation spots and remained their most consistent starter throughout the season, leading the team in every pitching category except in ERA. In 2016, De La Rosa opened the season in the Diamondbacks' rotation but suffered elbow injuries all year. In September, the team elected to end De La Rosa's season early. He was non-tendered by Arizona on December 2, 2016. On January 3, 2017, De La Rosa and the Diamondbacks agreed to a minor league contract. On June 23, De La Rosa's contract from AAA was picked up by the Diamondbacks. In August, it was determined that he needed a second Tommy John Surgery after suffering an injury. He was released by the Diamondbacks on September 1. He resigned a two year minor league deal on November 7, 2017. On June 20, 2019 he was granted his release by the Diamondbacks so he could play in Japan.
Yomiuri Giants
On June 27, 2019, he signed with the Yomiuri Giants of Nippon Professional Baseball. On November 26, 2019, De La Rsa signed a 1-year extension to remain with the Giants.
