He played in Major League Baseball (MLB) for the Oakland Athletics, Cincinnati Reds, Seattle Mariners, and Washington Nationals.

His father, Rory, served in the Air Force, and moved his family to California and later Tabernacle Township, New Jersey, where Doolittle grew up.

[5] In 2005 and 2006, Doolittle played for the collegiate USA national baseball team, again serving as both a pitcher and batter.

He was close to returning to Triple-A in the summer of 2010, but popped a tendon in his right wrist during a swing, requiring more rehabilitation and ending a comeback attempt.

With all three teams, he allowed only 2 earned runs and two extra base hits, both doubles, while striking out 48 batters in 25 innings.

[26] He quickly became a key bullpen piece as the top lefty specialist, earning his first career save on July 21 against the New York Yankees.

[30] In the postseason, he took the loss in Game 4 of the ALDS after giving up a game-tying home run to Víctor Martínez of the Detroit Tigers.

[2][32] Doolittle and righty Luke Gregerson entered the regular season as late-inning setup pitchers for new closer Jim Johnson.

[37] He had a poor showing in his third straight postseason, blowing a save in the month inning of a Wild Card Game loss to the Kansas City Royals.

[17] On June 7, while on rehab assignment with the Triple-A Nashville Sounds, Doolittle pitched the seventh inning of a combined no-hitter, immediately following starter Chris Smith.

[49] On July 16, 2017, the Athletics traded Doolittle and Madson to the Washington Nationals for reliever Blake Treinen and prospects Jesús Luzardo and Sheldon Neuse.

[51] After taking a Southwest Airlines flight from Oakland to join the Nationals in Anaheim, Doolittle earned his first save with his new team on July 18.

"[52] Doolittle, Madson, and fellow mid-season trade acquisition Brandon Kintzler improved the Nationals' bullpen, which had the lowest ERA in the last three innings of a game in the NL following the trade for Doolittle and Madson, en route to an NL East division title.

[53] He earned his first postseason save in Game 2 of the National League Division Series, pitching a scoreless ninth inning.

He had 22 saves in 23 in opportunities in his first 35 games,[55] but on July 11 was placed on the disabled list with inflammation on a toe on his left foot.

[6] However, after allowing three home runs in a blown saves against the Milwaukee Brewers on August 17,[61] Doolittle was placed on the injured list with knee tendinitis.

He had a four-out save in Game 1 of the National League Championship Series,[64] in the closer's role because Hudson was on paternity leave.

[72] Doolittle appeared in 45 games for the Reds in 2021, with a 3–1 record and 1 save in 5 opportunities, posting a 4.46 ERA with 41 strikeouts 38+1⁄3 innings.

[78][79] After six scoreless appearances, he was placed on the injured list on April 20 and underwent internal brace surgery on the ulner collateral ligament in his elbow in July, which ended his season.

[81] He was not able to fully come back from his elbow surgery and suffered a knee strain in late June, sending him to the injured list for the final time in his career.

[82][17] In 11 minor league games before the knee injury, pitching for the Single-A Fredericksburg Nationals, High-A Wilmington Blue Rocks, Double-A Harrisburg Senators, and Triple-A Rochester Red Wings, Doolittle had a 5.91 ERA.

[86] Doolittle threw his fastball 87 percent of the time, the second highest frequency of any pitcher during his career, trailing only Jake McGee, and the sixth-most since pitch-type data was tracked starting in 2002.

[92] Regarding his charity work, Doolittle told The New York Times in 2016: "When I was a kid, I remember my parents would say, 'Baseball is what you do, but that's not who you are' — like that might be my job, but that's not the end-all, be-all.

[94] In June 2015, when the Oakland Athletics Pride Night received backlash from some fans for the team's support of LGBT rights, Doolittle and then-girlfriend Eireann Dolan bought hundreds of game tickets, which they donated to local LGBT groups and raised an additional $40,000 in donations.

[102] In October 2016, Doolittle was one of several professional athletes to denounce Republican presidential candidate Donald Trump's comments about non-consensual groping of women as not being wikt:"locker room talk".

[103] In 2019, the Washington Post reported that, because of then-president Trump's actions, Doolittle would not attend a ceremony at the White House following the Nationals' World Series win.

[98][105] Doolittle spoke to youth baseball players as part of MLB's "Shred Hate" anti-bullying campaign.

[91] Doolittle and Eireann Dolan married on October 2, 2017, eloping the day after the Nationals' last game of the regular season.

[110] While traveling for away games, Doolittle made it a practice to seek out independent bookstores, and then share his visits on social media.

"[111] In an interview with Librarian of Congress Carla Hayden, Doolittle said that one of his favorite authors is Octavia E. Butler and in particular he is a fan of Parable of the Sower.