He attempted to walk on to the Arkansas Razorbacks baseball team in the National Collegiate Athletic Association (NCAA), but was denied the opportunity to try out.

Czyz recommended Treinen to Ritchie Price, the head coach of the South Dakota State Jackrabbits baseball team.

[10] During the 2014 Washington Nationals season, Treinen appeared both as a starting pitcher and out of the bullpen, with his fastball clocked as high as 98 miles per hour (158 km/h).

[12] For the 2015 season, Treinen started the year in the Nationals bullpen, with the off-season acquisition of Max Scherzer creating a crowded rotation picture.

Manager Matt Williams, dealing with injuries to his veteran relievers, began inserting Treinen into high-leverage, late-game situations in early April, occasionally setting up for closer Drew Storen.

Treinen led the National League in groundballs induced with 65.9% on the season and ranked highly in inherited runners stranded and soft contact created, among other metrics.

[18] Treinen was frequently used in situations when another Nationals pitcher had allowed one or more baserunners and manager Dusty Baker was seeking a double play ball, a role in which he excelled with his high-90s sinker.

[21] On Opening Day, Treinen pitched a perfect inning in the top of the ninth against the Miami Marlins with two strikeouts to end the game, earning the save, the second of his career.

[24] After just a couple of weeks as the closer in which he posted a 7.11 ERA, Treinen was removed from the role in favor of Shawn Kelley and later Koda Glover.

[26][27] But with both Kelley and Glover on the disabled list, fellow setup men Enny Romero and Matt Albers unavailable, and acting manager Chris Speier in need of a reliever to close out the ninth inning of a 4–2 game against the Chicago Cubs on June 29, Treinen was called upon for his first save opportunity since being demoted from the position of closer.

[28][29] On July 16, 2017, the Nationals traded Treinen back to the Athletics, along with Sheldon Neuse and Jesus Luzardo, for Sean Doolittle and Ryan Madson.

[33] On June 21, 2019, Treinen was placed on the 10-day injured list with soreness in his right shoulder after an appearance against the Tampa Bay Rays in which he gave up three runs without recording an out.

[36] The start of the 2020 season was delayed to late July by the COVID-19 pandemic, but Treinen appeared in 27 games for the Dodgers (3rd in the NL), with a 3–3 record with one save and a 3.86 ERA.

[39] Despite the injury, the Dodgers announced on May 22 that they had signed him to a one-year, $8 million, extension covering the 2023 season and included a conditional option for 2024.

[41] On November 11, 2022, Treinen underwent right shoulder labrum and rotator cuff repair surgery, with an estimated 10 month recovery.

[48] In 2023, Treinen criticized the Dodgers organization for including the Sisters of Perpetual Indulgence, an LGBT charity, in their annual Pride Night event, saying that it "disenfranchises a large community and promotes hate of Christians and people of faith.