The team announced on Tuesday that they had placed Realmuto on the 10-day injured list, retroactive to Monday, with right knee pain.
Realmuto is scheduled to undergo right knee meniscectomy surgery on Wednesday in Philadelphia.
In his absence, the Phillies have recalled catcher Rafael Marchán from triple-A Lehigh Valley.
There was no indication from the team as to how long Realmuto would ultimately be out.
Over his first 51 games of the season, Realmuto has slashed .261/.309/.411 with a .720 OPS.
His seven home runs are tied for the most among all National League catchers, and he ranks third in runs scored (28) and fourth in extra-base hits (16).
Realmuto posted a career-high 17-game hitting streak earlier this season, which was the longest for a Phillie who primarily played catcher since at least 1900.
Additionally, his 2.84 catcher's ERA is first among all NL catchers.
Marchán, who will be filling Realmuto's spot on the 26-man roster for the time being, has had one major league stint with the Phillies this season after being added as the 27th player for the London Series, though he did not appear in either game.
In 13 combined games between the IronPigs and single-A Clearwater, including eight rehab appearances, Marchán slashed .233/.382/.395 with one double, two home runs, eight RBI, 10 walks, and four runs scored.
Marchán was signed by the Phillies as an amateur free agent back in July 2015.