On September 16, 2014, the Yankees promoted Pirela to the major leagues. He made his major league debut on September 22, hitting a triple in his first at bat, and a single later in the game. In seven games with the Yankees in 2014, he batted.333 with two triples and three RBIs. On September 25, 2014, Pirela's single in the Yankees' last home game of the season against the Baltimore Orioles set up Derek Jeter's walk-off hit in his final at-bat at Yankee Stadium. Pirela singled to leftfield and subsequently replaced by pinch-runner Antoan Richardson, who scored the winning run on Jeter's hit. Pirela suffered a concussion on March 22, 2015, in a spring training game against the New York Mets while playing center field. He ran into the outfield wall while chasing a fly ball. On April 2, he was placed on the 7-day disabled list to begin the season due to his concussion, and a week later he was transferred to the 15-day disabled list. On June 7, he hit his first major league home run against the Los Angeles Angels. He batted.256 with 1 RBI in 18 games before he was optioned to Scranton/Wilkes-Barre on June 10.
On November 11, 2015, the Yankees traded Pirela to the San Diego Padres for minor league pitcher Ronald Herrera. He began the 2016 season with the El Paso Chihuahuas of the Class AAA Pacific Coast League, and was promoted to the Padres on April 22. Pirela played in 15 games with the Padres in 2016, making nine starts at second base and one in right field, before being optioned to El Paso when Yangervis Solarte was activated from the disabled list on May 21. Pirela was shut down in June with an Achilles tendon injury after playing in only 35 minor league games on the season. He had originally hurt the Achilles in the spring and it affected his performance all season. Pirela was non-tendered in the 2016 offseason, and became a free agent. He signed a minor league contract with the Padres on December 13, 2016. Pirela began the 2017 season with El Paso, where he batted.331/.387/.635 with 13 home runs in 181 at bats. The Padres promoted Pirela to the Major Leagues on June 6. Pirela was slotted into left field and impressed with his bat, securing the number three spot in the batting order by August and holding onto the left field position after Opening Day left fielder Travis Jankowski came off the disabled list. Pirela saw his season ended in mid-September with a sprained finger, but he led the Padres regulars in batting average, on-base percentage, and slugging percentage, and was the Padres nominee for the Hank Aaron Award. He finished 2017 with a.288/.347/.490 batting line with 10 home runs and 40 RBIs in 83 games, playing 72 games in the outfield, 7 games at second base, 5 games at first base, and 1 game at third base. Pirela began 2018 as a starter for the Padres, but he saw his playing time significantly shrink as the season progressed. He began the season as the regular left fielder, but took over second base from Carlos Asuaje in May as Franchy Cordero moved over to left. When Asuaje was recalled from El Paso on July 1 and moved back onto second base, Pirela had no regular position but continued to appear as a pinch hitter and utility player. In 2018 with San Diego he batted.249/.300/.345 with 5 home runs and 32 RBIs in 146 games. Pirela started the 2019 season in AAA but was recalled to the majors on April 19, 2019, before being placed on the injured list with an oblique strain five days later. For El Paso he batted.353/.401/.674 with 18 home runs in 221 at bats. He was designated for assignment on July 22.
Philadelphia Phillies
On July 27, 2019, the Padres traded Pirela to the Philadelphia Phillies in exchange for cash considerations. With the AAA Lehigh Valley Ironpigs he batted.281/.331/.455 with 4 home runs and 14 RBIs in 121 at bats. With the Phillies he batted.235/.316/.471 with one home run and two RBIs in 17 at bats. In the major leagues through 2019, Pirela had played 127 games at second base, 105 games in left field, 14 games at first base, 14 games in right field, and one game at third base.
Hiroshima Toyo Carp
On November 2, 2019, Pirela signed with the Hiroshima Toyo Carp of Nippon Professional Baseball.
Playing style
Pirela is a free-swinger in the batter's box, with a 6.4% walk rate in the major leagues. Despite this, he has kept his strikeout rate at 19.9%. In the field, Pirela has appeared in the majors at first base, second base, third base, and in both of the outfield corners. His nickname is "La Cucaracha," a nod to both his Hispanic heritage and the fact that Padres General Manager A. J. Preller designated several players for assignment before Pirela; fans believed the other players were more deserving of roster spots.
