Rosario began his professional career with the Los Angeles Angels of Anaheim organization in 2005. The St. Louis Cardinals promoted Rosario to the major leagues on July 6, 2016. He played 11 seasons in Minor League Baseball before making his major league debut July 9, 2016, against the Milwaukee Brewers. He singled and batted in a run in his first MLB at-bat in an 8−1 win. He elected free agency on November 6, 2017.
On January 5, 2018, Rosario signed a minor league contract with the Arizona Diamondbacks that includes a non-roster invitation to spring training. He elected free agency on November 3, 2018. On January 9, 2019, he re-signed with the Diamondbacks to a minor league deal. He was assigned to AAA Reno Aces to start the 2019 season. He elected free agency on November 7, 2019. On January 10, 2020, Rosario again re-signed with the Diamondbacks to a minor league deal for the 2020 season. On May 22, 2020, Rosario was released by the Diamondbacks organization. On July 27, 2020, Rosario re-signed with the Diamondbacks on a minor league contract. He became a free agent on November 2, 2020.

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