At the age of 10, Betances attended the perfect game of then-Yankees pitcher David Wells in 1998, sitting with the Bleacher Creatures.

[5] Betances attended Progress High School within the Grand Street Campus in Brooklyn, New York.

[6] As a freshman, Betances was 6 feet 4 inches (1.93 m) tall, and could throw a fastball as fast as 85 miles per hour (137 km/h).

The Yankees selected Betances in the eighth round of the draft and gave him a $1 million signing bonus to forgo his commitment to Vanderbilt.

He struggled with Tampa, as he pitched to a 2–5 win–loss record with a 5.48 earned run average (ERA) in 11 games started, before suffering an elbow injury in June.

[14] Betances began the 2010 season with Tampa,[12] and received a midseason promotion to the Trenton Thunder of the Class AA Eastern League.

[17] Betances had a pitching session in the street in front of his Teaneck, New Jersey home with his brother before joining up with the Yankees in Anaheim.

[22] After pitching to a 1.46 ERA with 63 strikeouts in 49+1⁄3 innings as a relief pitcher with Scranton/Wilkes-Barre, the Yankees recalled Betances on August 11.

[23] Betances was optioned to Triple-A Scranton/Wilkes-Barre on August 15[24] and brought back up to the majors on September 1, 2013, when rosters were expanded.

In 2014, Betances made 70 appearances out of the bullpen with a 5–0 record, a 1.40 ERA, and his 135 strikeouts led the majors amongst all relief pitchers.

Betances finished in 3rd place in voting for the American League Rookie of the Year Award, behind Angels pitcher Matt Shoemaker and White Sox first baseman Jose Abreu.

He became the first Yankees reliever in franchise history to reach the 100-strikeout club in back-to-back seasons, needing only 64 innings to do it this year.

[37] On August 24, Betances was ejected for the first time in his Major League career after hitting James McCann with a pitch.

[40] On March 19, 2019, it was announced by the team that Betances would start the season on the injured list due to a right shoulder impingement.

[41] He was transferred to the 60-day injured list, and was revealed that he was diagnosed with a bone spur behind his right shoulder, putting his chances of playing in 2019 in jeopardy.

[45] On June 30, it was announced that Betances would undergo season-ending surgery on his bothersome shoulder, ending his 2021 season at one inning of work.

With the money Betances received in his signing bonus, he purchased a house for his parents in Teaneck, New Jersey.