Descalso filed for a $1.65 million contract request following the season. The Cardinals and Descalso avoided arbitration and agreed to a one-year, $1.29 million contract on January 30, 2014. Descalso made his major league pitching debut against the Chicago Cubs in the top of the ninth inning with two outs on May 12, 2014. He threw two pitches, recording one out and allowing no hits. With a chance for increased playing time during interleague play against the Baltimore Orioles, he collected five hits in 10 at bats over an August 8–10 series.
Descalso signed a two-year deal with the Colorado Rockies on December 16, 2014. The deal totaled $3.6 million with the opportunity for another $1 million in performance bonuses. Descalso appeared in 101 games in 2015, hitting a career worst .205 with five home runs and 22 runs batted in. Descalso began the 2016 season on the disabled list with a broken hand suffered in spring training. In 2016, Descalso appeared in 99 games, bouncing back offensively by hitting .264 with a career-high 8 home runs and 38 runs batted in. Descalso served as a veteran presence on the Rockies, while also filling an important utility role, receiving time at six different positions over the course of his two seasons at Colorado.