Initially a starting pitcher, Britton converted to a closer and led the American League in saves in 2016 and was named to the AL All-Star team in 2015 and 2016.

[7] During baseball practice with the freshman team, he sustained fractures of the skull and clavicle and bleeding in the brain as a result of diving headfirst into concrete while attempting to catch a foul popup.

[8] The Baltimore Orioles selected Britton in the third round, with the 85th overall pick, of the 2006 Major League Baseball draft.

[12] Even though Britton was statistically the Orioles' best pitcher during spring training, he started the 2011 campaign in the minors, being optioned to the Norfolk Tides on March 29.

[13] Britton was recalled five days later on April 3, however, to replace the injured Brian Matusz in the starting rotation.

[14] Britton capped a season-opening three-game sweep of the Tampa Bay Rays by winning his MLB debut that same day in a 5–1 victory at Tropicana Field.

[17] He hit his first big league home run off Brandon Beachy in the third inning of a 5–4 victory over the Atlanta Braves at Turner Field on July 3.

There was speculation that the Orioles made the move to prevent him from getting a full year of major league service time and thus delaying his eligibility for free agency by a season.

[18] Britton finished his rookie campaign, appearing in 28 games (all starts), pitching to a 4.61 ERA, 1.45 WHIP and an 11–11 record.

The Orioles optioned Britton to their Triple-A affiliate Norfolk Tides on March 23 to start the 2013 season.

Britton made the opening day roster for the 2014 Orioles season and picked up his first win of the year pitching in relief against the Red Sox on March 31.

[21] On May 15, Britton earned his first career save, against the Kansas City Royals, pitching a perfect 9th inning.

[22] The Orioles would sweep the Detroit Tigers in the 2014 American League Division Series, with Britton earning a pair of saves, in games 2 and 3.

[citation needed] On June 9, Britton converted his 19th consecutive save to start the season, setting a new Orioles franchise record.

Britton extended his streak to 29 games to close out the first half of the 2016 season after converting 27 consecutive saves before the All-Star break.

Selected to the All-Star team for his second straight year, Britton pitched to a 2–1 record with a 0.72 ERA and 43 strikeouts in 372⁄3 innings.

On August 11, Britton set the MLB record for most consecutive relief appearances without allowing an earned run, which was thirty-nine up to that point.

[citation needed] On August 24, Britton allowed his first earned run in 44 appearances in a 10–8 win over the Washington Nationals, ending his MLB-record streak.

From the beginning of May to the end of the regular season, Britton pitched to an 0.16 ERA, holding hitters to a .160/.222/.195 slash.

Two days later, Britton shut the door on the Yankees to seal a 6–5 victory, helping the Orioles advance to 3–0 on the year.

On August 23, Britton's streak ended after he gave up two runs in the ninth inning to the Athletics, allowing them to tie the score.

He was placed on the 60-day disabled list to begin the season as he recuperated from the ruptured Achilles tendon injury he suffered in December.

On July 24, 2018, the Orioles traded Britton to the New York Yankees in exchange for Dillon Tate, Cody Carroll, and Josh Rogers.

On September 9, 2021, Britton underwent Tommy John surgery along with removal of bone chips in his pitching elbow.