Ureña was called up to the majors for the first time on April 13, 2015 to replace David Phelps. In his first major league start on May 26, 2015, against the Pittsburgh Pirates, he gave up five runs in innings and took the 5–1 loss. In 20 games with the Marlins in 2015, Ureña finished with a 1–5 record and a 5.25 ERA. In 2016, Ureña split time starting and in the bullpen, finishing the year with a 4–9 record and a 6.13 ERA in 28 games. In 2017, Ureña improved, appearing in 34 games with a 14–7 record, and a 3.82 ERA. He also hit a league-leading 14 batsmen with pitches. Ureña was named the Opening Day starter for 2018. On Opening Day against the Chicago Cubs on March 29, 2018, Ureña did not fare well as he surrendered a home run by Ian Happ on the first pitch he threw. He allowed five runs altogether in 4+ innings as the Marlins lost 4–8. Ureña started 16 games for the Marlins before landing on the disabled list with a shoulder injury. On August 15, 2018, he was ejected from a game against the Atlanta Braves after hitting Ronald Acuña Jr. on the elbow with the first pitch of the game, which led to the Braves' and Marlins' benches clearing. Acuña had hit a home run in his previous five games. Ureña received a six-game suspension for his role in the altercation. In his next start, Ureña threw a complete game against the Washington Nationals, giving up one run on two hits while striking out four batters. He ended the season going 6–0 in his final seven starts to go along with a 1.80 ERA. By posting a 3.82 ERA in 2017 and a 3.98 ERA in 2018, Ureña became just the sixth starting pitcher in Marlins history to post a sub-4.00 ERA in consecutive seasons, joining Pat Rapp, Kevin Brown, Dontrelle Willis, Josh Johnson, and Aníbal Sánchez. In 2019, Ureña became the eighth pitcher in Marlins history to make consecutive Opening Day starts. After beginning the season 0–3, he tossed quality starts in eight of his next nine outings, going 4–3 with a 2.95 ERA over that span. Following a start against the Atlanta Braves on June 7, 2019, Ureña was placed on the injured list with a herniated disc in his lower back. At the time of his injury, he was tied for twelfth in the MLB with eight quality starts.
Pitching style
According to a scouting report prepared for MLB's 2014 midseason prospect rankings, the eighth-ranked Ureña had "an above-average fastball that can touch the mid 90s", a change-up, and a breaking ball that is "a combination of a slider and a curve". He was said to have "above-average command". However, Ureña's command of the ball has dipped significantly since the start of the 2017 season with ESPN writers recognizing "a history of control problems," noting that in 2017, he hit 14 batters in 2017, tying in the MLB for hit batters, and as of hitting Ronald Acuña Jr. in 2018, had tied for second in the National League, hitting 10 batters.
