He has previously played for the St. Louis Cardinals, Toronto Blue Jays, San Francisco Giants, Chicago White Sox, and Kansas City Royals.

A native of Orlando, Florida, DeJong played college baseball at Illinois State University (ISU).

He made his MLB debut in 2017 with the Cardinals, and led National League (NL) shortstops in home runs that season with 25.

[2] After the 2014 season, the Pittsburgh Pirates chose DeJong in the 38th round of the Major League Baseball (MLB) draft as a catcher.

He had a 3.74 GPA, and planned to attend medical school in the event a career in professional baseball did not work out.

[22][21] To begin the 2017 season, the Cardinals assigned DeJong to the Memphis Redbirds of the Triple–A Pacific Coast League (PCL).

The Cardinals promoted DeJong to the major leagues on May 28, 2017, as they moved second baseman Kolten Wong to the disabled list (DL).

[23] DeJong made his major league debut on May 28, 2017, playing at Coors Field against the Colorado Rockies.

[24] On July 8 against the New York Mets, he set both a Cardinals shortstop and a number eight hitter record with four extra base hits in one game, including three doubles and one home run.

[28] On August 19, DeJong hit his 20th home run, off Juan Nicasio, becoming the fourth Cardinals rookie to do so, in a 6−4 loss to the Pittsburgh Pirates.

[29] DeJong finished his 2017 rookie campaign batting .285./325/.532 with 65 RBIs, and 25 home runs — the latter more than any other National League shortstop that year.

[21] On March 5, 2018, DeJong agreed to a six-year contract extension with St. Louis through the 2023 season worth a guaranteed total of $26 million.

[44] Batting .261 with 13 home runs and 36 RBIs, DeJong was selected to represent the Cardinals at the All-Star Game in Cleveland.

[45] On July 24, while playing the Pittsburgh Pirates at PNC Park, DeJong hit three home runs, becoming the first St. Louis shortstop ever to accomplish that feat.

[47] Per Baseball-Reference.com, he led all National League fielders in defensive Wins Above Replacement (WAR) with 3.3[48] and assists (435), and NL shortstops in putouts (211) and double plays turned (119).

[51] He returned to the team on August 23 and finished the shortened season hitting .250/.322/.349 with three home runs and 25 RBIs in 45 games.

[55] After struggling at the plate and the positive play of Edmundo Sosa, DeJong eventually moved into a reserve role.

[56] However, he shortly moved back into a starting role after Sosa sustained a wrist injury in early September.

On May 10, 2022, DeJong was demoted to the Triple-A Memphis Redbirds after batting .130/.209/.208 with one home run over 24 games to start the season.

[59][60] On July 30, the Cardinals traded Sosa to the Philadelphia Phillies and DeJong was recalled from Memphis the same day and placed into the starting lineup as their shortstop.

On July 30, 2024, the White Sox traded DeJong to the Kansas City Royals in exchange for pitcher Jarold Rosado.

[9] After the 2017 season, DeJong participated in a scientific study as laboratory assistant with Lawrence Rocks exploring the effects of differing temperatures on the flight of the path of the baseball.