On August 17, 2009, Matzek agreed to a $3.9 million signing bonus to join the Colorado Rockies organization. He did not pitch professionally in 2009. Prior to the 2010 season he was ranked by Baseball America as the 23rd best prospect in baseball. Playing for Single-A Asheville, he compiled a record of 5-1 with an earned run average of 2.92 and 88 strikeouts in 89.1 innings of work over 18 starts. However, he struggled with control, walking 62 and hitting 4 batters. Prior to 2011 Baseball America ranked him as the 32nd best prospect. He started the season with the High-A Modesto, but struggled mightily, going 0-3 with a 9.82 ERA with 46 walks in 33 innings. He was demoted back to Asheville, where he made three rather unsuccessful starts before going on a "little mental break" after his start on June 17. He returned to Asheville on July 20 to finish the season. He went 5-4 with a 4.36 ERA with the Tourists in 2011, striking out 74 and walking 50 in 64 innings. Matzek started the 2012 season with Modesto. He was a mid-season All-Star in the California League, going 4-3 with a 3.24 ERA before the break, striking out 83 and walking 52 in 75 innings. His second half was slightly worse than the first, and he finished 2012 going 6-8 with a 4.62 ERA, striking out a league-leading 153 and walking a league-leading 95. In 2013, he pitched for Double-A Tulsa. He was also a mid-season All-Star in the Texas League, going 3-6 with a 4.04 ERA before the break, striking out 55 and walking 40 in 75.2 innings. His second half was slightly better this year, and he finished 2013 with the Drillers 8-9 with a 3.79 ERA, striking out 95 and walking 76 in 142.1 innings. After the year, Matzek pitched for the Salt River Rafters of the Arizona Fall League, where in 10 games of relief, he went 1-1 with a 3.86 ERA and a 1.457 WHIP, earning him a selection to the AFL Fall Stars Game. Matzek was added to the Rockies 40-man roster on November 20, 2013. He started the 2014 season with Triple-A Colorado Springs. He made 12 starts for the SkySox before earning his first promotion to the major leagues, going 5-4 with a 4.05 ERA, striking out 61 and walking 31 in 66.2 innings. Matzek was promoted to the Colorado Rockies on June 11, 2014, to replace Eddie Butler, who went on the disabled-list after his major league debut. Matzek made his major league debut that day, giving up 2 runs on 5 hits with 7 strikeouts and 0 walks in 7+ innings in an 8-2 victory against the Atlanta Braves. He also recorded his first hit off of Julio Teherán, an infield-single in the 7th inning, and he later scored. Matzek got his first career complete game shutoutSeptember 5, 2014 vs the San Diego Padres. In the game, he gave up 3 hits and the Rockies won the game 3-0. At the end of the season, Matzek won 6 games while losing 11 in 19 starts. He began the 2015 season in the Rockies rotation, but after experiencing control problems he was sent down to Triple-A. He would spend the rest of the season in Triple-A. After having surgery towards the end of the 2015 season, Matzek began the 2016 season on the disabled list. He was outrighted off the roster at midseason and was released at the end of the season.
On April 12, 2018, Matzek signed with the Texas AirHogs of the independent American Association. In innings, he struck out 93 batters but walked 66 batters.
On January 15, 2019, Matzek signed a minor league contract with the Arizona Diamondbacks following a showcase with Driveline baseball. He was released on May 16, 2019.
Second stint with AirHogs
On June 9, 2019, Matzek signed with the Texas AirHogs of the American Association. He had a 2.64 ERA and 53 strikeouts in innings pitched.
Atlanta Braves
On August 14, 2019, Matzek's contract was purchased by the Atlanta Braves. Matzek began his stint with the Mississippi Braves, their AA affiliate. After just one appearance in which he pitched 2.1 innings and had five strikeouts, Matzek was promoted to the Braves AAA affiliate, the Gwinnett Stripers. For the 2020 season, Matzek made the Opening day roster, marking his first appearance in the majors since 2015.
