He played various sports as he grew up, helping both the baseball and gridiron football teams of Carl Albert High School win state championship titles.

Although he served as the baseball team's shortstop throughout his high school career, a scout for the Miami Marlins encouraged Realmuto to become a full-time catcher.

The Marlins selected him in the third round of the 2010 MLB Draft, and Realmuto chose to sign with the team rather than honor a commitment to playing college baseball at Oklahoma State.

He spent the next several seasons in the Marlins' farm system, building strong relationships with pitchers and working on picking off attempted base stealers.

[3] Because his father David was often busy coaching his older sisters' softball teams, Realmuto's mother Margaret often drove him to his Little League Baseball games and various other sporting matches.

[9] Realmuto also received the Bob Colon Scholarship, presented annually by The Oklahoman and the Jim Thorpe Association to the top male high school scholar-athlete in the greater Oklahoma City area.

[9] Although he had previously committed to play college baseball at Oklahoma State on an athletic scholarship, Realmuto chose to accept the Marlins' offer, which included a $700,000 signing bonus.

[11] He excelled both offensively and defensively in his 96 games with Greensboro; in addition to batting .287 with 12 home runs and 49 RBIs, Realmuto successfully picked off 42 percent of attempted base stealers.

Realmuto also helped take the Grasshoppers to a South Atlantic League championship title, recording a critical RBI in the final round against the Savannah Sand Gnats.

There, Realmuto was paired with up-and-coming pitcher José Fernández, a partnership that the Marlins envisioned would form the backbone of their future major league roster.

[13] Realmuto was one of three Hammerheads named to the 2012 Florida State League All-Star Game, alongside outfielders Christian Yelich and Marcell Ozuna.

[26] Realmuto made his major league debut on June 5, recording three RBIs against Jake Odorizzi in an 11–6 rout of the Tampa Bay Rays.

[10][30] Realmuto was meant to serve as a backup catcher to Saltalamacchia, with several opportunities to start behind the plate as Mathis waited four to six weeks for his fractured finger to heal.

[32] He hit his first major league home run the following month, a two-run shot against Rubby De La Rosa in the seventh inning of a 3–2 loss to the Arizona Diamondbacks on May 18, 2015.

[29] With the offseason acquisition of backup catcher A. J. Ellis, the Marlins expressed interest in allowing Realmuto to play other positions during the 2017 season, such as first base.

[41] Later that year, Realmuto hit his second career inside-the-park home run, tying the game in an eventual 9–8 defeat of the Philadelphia Phillies on August 24.

[29] At the end of the season, Realmuto won the Jeff Conine Award, given annually by the Miami chapter of the Baseball Writers' Association of America to the player "whose commitment to the game is embodied in his integrity and unselfish play".

[52] At the arbitration deadline on January 11, 2019, Realmuto agreed to a $5.9 million contract with the Marlins, including bonuses for each All-Star selection, Silver Slugger, and Gold Glove Award.

On February 7, 2019, the Marlins traded Realmuto to the Phillies in exchange for catcher Jorge Alfaro, pitching prospects Sixto Sánchez and Will Stewart, and $250,000 in international bonus slot money.

[57] On November 3, Realmuto won his first career Gold Glove, joining Bob Boone and Mike Lieberthal as the third Phillies catcher to win the award.

[59] Four days later, he received his second Silver Slugger, becoming the first Phillies player to win the award since Chase Utley ten years prior.

[62] He was an early star in the Phillies' disappointing season; although the team posted a 5–9 record in their first 14 games, Realmuto collected eight home runs within the same span.

[29] With the knowledge that Realmuto was on track to become a free agent at the end of the 2020 season, both Phillies fans and teammates began using the phrase "Sign J. T." to pressure managers into offering him a new contract.

[70] Although fans were not allowed inside Citizens Bank Park due to restrictions imposed by the COVID-19 pandemic, many would stand outside the ballpark gates to chant, "Sign J.

[73] He did not return to spring training until a March 23 Grapefruit League game against the Toronto Blue Jays, in which he hit a home run during his first at bat.

[74] Realmuto suffered another injury that May, ultimately missing 11 games after a wild pitch from David Hale caused a bone bruise on his left hand.

[37] In game 4 of the 2022 National League Division Series, against the Atlanta Braves, Realmuto became the first ever Phillies player, and first ever catcher, to hit an inside the park homerun in the postseason.

Although pop time has been criticized by some sabermetrics analysts for not considering accuracy of throws, Realmuto also led all major league catchers in caught stealing rate, picking off 44 percent of attempted base runners.

He turned 30 before the start of the 2021 MLB season, a point at which many major league catchers begin to experience a downturn in productivity and increased injury.

[103] In 2019, Realmuto and pitcher Aaron Nola were selected as the Phillies representatives for Garth Brooks' "Home Plate Project", an organization designed to fight childhood hunger.