[4] His mother, Riquelma Ramos, learned to speak French while living in Montreal and later moved with him to the Dominican Republic, where Vladimir Jr. spent most of his early childhood.

Guerrero split time between Santiago with his mother, Don Gregorio with his uncle Wilton and, during the summer, in the United States with his father.

[12] Guerrero made his professional baseball debut with the Rookie Advanced Bluefield Blue Jays on June 23.

[14] On August 12, Guerrero recorded his first multi-home run game, hitting two solo shots in an 18–5 win against the Pulaski Yankees.

[24] In a game against the Clearwater Threshers on August 31, Guerrero hit a home run to give the Blue Jays a 5–3 victory, with the win ensuring Dunedin would make the Florida State League playoffs.

[25] Guerrero finished the 2017 regular season with a .323 batting average, 13 home runs, and 76 RBI in 119 games played.

[17] Entering the 2018 season, Guerrero was considered the top prospect in the Blue Jays organization by MLB and Baseball America.

[28][29] On March 23, Blue Jays team president Mark Shapiro announced that Guerrero would begin the season with the Double-A New Hampshire Fisher Cats.

[31] On June 4, Guerrero was named the Eastern League's Player of the Month after hitting .438 with nine home runs and 28 RBI in May.

[33] On July 28, it was announced that Guerrero would be promoted to the Triple-A Buffalo Bisons following his father's induction into the National Baseball Hall of Fame and Museum.

[34] On August 30, the Blue Jays added Guerrero to the roster of the Surprise Saguaros of the Arizona Fall League (AFL).

[35] Entering 2019 spring training, questions arose as to whether the Blue Jays organization would have Guerrero on the Opening Day roster, or seek to manipulate his MLB service time by assigning him to the minors to begin the season.

[36][37] On March 10, the Blue Jays announced that Guerrero had suffered an oblique strain two days earlier and was ruled out for the rest of spring training.

Guerrero was considered the top prospect in all of professional baseball prior to being called up,[39][40] and was hitting .367/.424/.700 with three home runs and eight RBIs during an eight-game stint with Buffalo in 2019.

[41] He went hitless in his first three at-bats against the Oakland Athletics before hitting a double in the bottom of the ninth inning and exiting for a pinch runner.

[43] On May 14, against the San Francisco Giants in Oracle Park, Guerrero hit his first major league home run in the first inning off Nick Vincent.

He hit two more home runs in the following series against the Chicago White Sox, including one that bounced off the glove of center fielder Leury Garcia and over the wall.

"[53] Guerrero opened the 2021 season as the Blue Jays primary first baseman while also getting routine starts at the designated hitter position.

On April 27, 2021, Guerrero had his first career three-homer game, including a grand slam against Washington Nationals starter Max Scherzer, to go along with 7 RBI on the day.

[55] He stated that he was looking forward to playing in the All-Star Game but would like to use the time to otherwise regroup and "refresh mentally" for the second half of the season.

[65] During an April 13 game against the New York Yankees, Guerrero hit a home run off Gerrit Cole and subsequently had his hand stepped on by Aaron Hicks during a play at first base.

[68] In 2022, Guerrero led the major leagues in double plays grounded into (26), and batted .274/.339/.480 with 32 home runs, 97 RBIs, and 116 strikeouts.

Defensively, scouts were unsure if he could remain at third base at the major league level, but he has shown the potential to develop into a passable defender.