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 RBI. The Cubs would eventually win the World Series, effectively ending their 108-year long drought. La Stella had one at bat in the postseason and won his first world championship. 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 RBI 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, La Stella was traded 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.