He previously played for the Baltimore Orioles, Atlanta Braves, Cincinnati Reds, and San Francisco Giants.

[4] The Los Angeles Dodgers selected Gausman in the sixth round of the 2010 Major League Baseball Draft, but he did not sign.

[9] In an interview with Jake Arrieta ten years later, Gausman said, "That's probably the one thing in baseball that I constantly look back on.

The Orioles promoted Gausman to the major leagues to make his debut in Toronto against the Blue Jays on May 23, 2013.

[18] On June 7, 2014, Gausman earned his first win as a starting pitcher, going seven innings against the Oakland Athletics, allowing only one run, walking one, and striking out six.

[19] Following the best outing of his young career, Gausman pitched against the AL East leading Toronto Blue Jays where he went six innings, again allowing one run and striking out three.

[22][23] Gausman finished the 2014 campaign having made 20 starts, with one complete game (five innings, due to rain), posting a 3.57 ERA and a 7–7 win–loss record.

He made his season debut on April 25 against the Rays, earning a tough loss after going five innings and giving up one run on three hits.

Following this start, he threw eight scoreless innings in a 1–0 victory over the Red Sox, improving to 8–10 on the year and lowering his ERA to 3.43.

His 8.716 K/9 and his 3.706 K/BB were both 10th in the AL.[26] On March 28, 2017, Gausman was named the Orioles' Opening Day starting pitcher for the first time in his career.

On May 3, Gausman was ejected for the first time in his Major League career after hitting Xander Bogaerts with a pitch.

[28] On July 29, Gausman pitched the longest outing of his career against the Texas Rangers, going 82⁄3 shutout innings while striking out eight batters and earning the victory.

[29] His 8.630 K/9 was 10th in the AL.[26] Before the 2018 season, Gausman changed from his old number of 39 to 34, in honor of the late former Toronto Blue Jays and Philadelphia Phillies pitcher, and fellow Coloradan Roy Halladay.

[31][32] On July 31, 2018, Gausman along with Darren O'Day, was traded to the Atlanta Braves in exchange for minor leaguers Brett Cumberland, Jean Carlos Encarnacion, Evan Phillips, Bruce Zimmermann, and international signing money.

[35][36] On May 3, 2019, Gausman was ejected from a game against the Miami Marlins by umpire Jeff Nelson for throwing behind José Ureña.

[47] In an appearance against the St. Louis Cardinals on August 18, Gausman struck out all six batters he faced, including tossing his second career immaculate inning.

On a full count, he hit his first career sacrifice fly, scoring Brandon Crawford to win the game.

[55] In the regular season in 2021, Gausman was 14–6 with a 2.81 ERA (6th in the NL), in a National League-leading 33 starts he pitched 192 innings (5th) and had 227 strikeouts (4th).

After a 2023 season in which Gausman had a 3.16 ERA over 185 innings and an AL-best 237 strikeouts, he went on to place third in 2023 Cy Young Award voting.