On July 26, 2011, Cowgill was called up from the Triple–A Reno Aces.[7]
He hit his first career major league home run as a Diamondback, on August 28, 2011, against the San Diego Padres.[8]
On December 18, 2012, the Athletics traded Cowgill to the New York Mets for Jefry Marté.[10]
Cowgill hit the first grand slam for the Mets on Opening Day in 18 years when he hit one in the 7th inning against the San Diego Padres.
On June 24, 2013, the Mets traded Cowgill to the Angels in exchange for minor league outfielder Kyle Johnson. On June 10, 2014, Collin Cowgill hit his first walk-off home run in the bottom of the 14th inning to beat the Oakland A's 2–1.
Cleveland Indians
Cowgill was traded from the Angels to the Cleveland Indians for cash considerations on December 2, 2015. He played in nine games for the Indians, including opening day, before being optioned to the minor league Columbus Clippers. The Indians designated Cowgill for assignment on September 1, 2016, and outrighted him to Columbus on September 2.
Cowgill elected free agency on October 5, 2016.
San Diego Padres
Cowgill signed a minor league contract with the San Diego Padres in 2017, that included an invitation to spring training. He was released on August 12, 2017.
Philadelphia Phillies
On February 8, 2018, Cowgill signed a minor league contract with the Philadelphia Phillies organization. In 93 games for the Triple–A Lehigh Valley IronPigs, he batted .230/.309/.408 with 12 home runs and 41 RBI. Cowgill elected free agency following the season on November 2.[11]
Washington Nationals
On February 21, 2019, Cowgill signed a minor league contract with the Washington Nationals. In 84 games for the Triple–A Fresno Grizzlies, he slashed .228/.330/.440 with 12 home runs, 34 RBI, and eight stolen bases. Cowgill elected free agency following the season on November 4.[12]
On February 17, 2020, Cowgill signed a minor league deal with the Seattle Mariners. Cowgill became a free agent after the season.