Thomas Frank La Stella was born in Westwood, New Jersey, on January 31, 1989, to Jane and Phil La Stella. He and his two siblings grew up in nearby Closter, New Jersey. He is of Italian descent.

La Stella attended Saint Joseph Regional High School in Montvale, New Jersey. He played baseball in high school, but quit after his junior year, citing burnout. He enrolled at St. John’s University, where he played college baseball for the St. John’s Red Storm for one year, before he transferred to Coastal Carolina University to play for the Coastal Carolina Chanticleers. La Stella appeared in 125 games (all starts) for the Chanticleers in 2010-2011 and batted .388 with 28 home runs and 136 runs batted in (RBIs). He committed 12 errors in 509 chances for Coastal Carolina, resulting in a .976 fielding percentage. In 2010, he played collegiate summer baseball in the Cape Cod Baseball League for the Bourne Braves.

The Atlanta Braves selected La Stella in the eighth round of the 2011 MLB draft. He signed with the Braves and spent the rest of the 2011 season with the Rome Braves of the Class A South Atlantic League. In 2012, he played for the Lynchburg Hillcats of the Class A-Advanced Carolina League. In 2013, he played for the Mississippi Braves of the Class AA Southern League. With the Mississippi Braves, La Stella had a .343 batting average in 81 games.

The Braves invited La Stella to spring training in 2014. He began the 2014 season with the Gwinnett Braves of the Class AAA International League, and debuted at the major league level on May 28, hitting two singles in his first game. La Stella hit his first major league home run on August 8, 2014, against Stephen Strasburg of the Washington Nationals. He finished the year with a .251 batting average in 93 games.

On November 16, 2014, the Braves traded La Stella, along with an international signing bonus slot, to the Chicago Cubs for Arodys Vizcaíno and three international signing bonus slots. La Stella made the Cubs’ Opening Day roster, but only played in two games before straining his right oblique on April 10, 2015. While rehabilitating at the minor league level with the Tennessee Smokies, La Stella suffered another oblique strain. He came off the disabled list in August, and was sent to the Iowa Cubs of the Class AAA Pacific Coast League. On August 24, he was recalled from Iowa and rejoined the major league club. In limited time with Chicago, La Stella was used mainly as a pinch hitter, a role in which he excelled. To increase his versatility, La Stella began playing third base during the regular season. In 33 games, La Stella hit .269/.324/.403, and started at third base during the National League Wild Card Game against the Pittsburgh Pirates.

After batting .295 for the Cubs in 2016, the Cubs optioned La Stella to Iowa on July 29, but he did not immediately report. The Cubs put La Stella on the temporarily inactive list. He agreed to report to Tennessee on August 17. Upon being recalled on August 31, La Stella stated that his refusal to report to the minors stemmed mainly from a lack of enjoyment for the game at the time of his demotion. In 74 games of the 2016 season, La Stella finished by batting .270/.357/.405 with two home runs and 11 RBIs. The Cubs won the 2016 World Series. La Stella had one at bat during the 2016 postseason. La Stella was on the roster for the 2016 National League Division Series, but was replaced by left-handed pitcher Rob Zastryzny for the 2016 National League Championship Series. Kyle Schwarber was given the final spot on the roster for the 2016 World Series.

In 2017, La Stella appeared in 73 games for the Cubs. He finished the year batting .288/.389/.472 with 22 RBIs and a career high of five home runs.

On July 20, 2018, La Stella pitched an inning and a third as a relief pitcher during a lopsided victory by the St. Louis Cardinals. On August 31, his 21st pinch-hit of the season, a single in the seventh inning in a game against the Philadelphia Phillies, broke the Cub record for pinch hits in a season previously shared by Thad Bosley and Dave Clark. The previous evening, La Stella had tied the record with a 2 run go-ahead home run against the Atlanta Braves. For the 2018 season, he batted .266/.340/.331 with one home run and 19 RBIs in 169 at bats.

On November 29, 2018, the Cubs traded La Stella to the Los Angeles Angels for future considerations. With 43 games played into the Angels season, La Stella was their regular second baseman and leadoff man with a slash line of .301/.388/.611. He was among the league leaders with 11 home runs and 25 RBIs. La Stella was chosen to appear in the 2019 All-Star Game, but on July 2, he fractured his tibia on a foul ball. Before the injury, La Stella had been one of the Angel’s most productive players. He had a .300 batting average with 16 homers and 44 RBIs in 78 games. La Stella did not return until late September, playing in two of the Angels’ final three games.

On August 28, 2020, the Angels traded La Stella to the Oakland Athletics for Franklin Barreto.

In 2020 between the two teams, he batted .281/.370/.449 with 5 home runs and 25 RBIs, and was by a wide margin the toughest AL ballplayer to strike out, averaging 16.3 at bats per strikeout. He also led all AL second basemen in errors, with four.