Coach Sean McDermott made the announcement Tuesday, adding that there is no timetable for Kroft's return.
It's the same foot Kroft broke last season when he was the Cincinnati Bengals, an injury that sidelined him for 11 games.
Meanwhile, wide receiver Cole Beasley and center Mitch Morse, two other prominent free-agent signings by the Bills this offseason, also aren't participating in OTAs. McDermott said both players underwent core muscle surgeries a few weeks ago and are not cleared to participate.
Kroft was expected to be the Bills' starting tight end after signing a three-year, $18.75 million contract with the team in free agency. He received $8.3 million guaranteed.
He started 35 games overall for the Bengals, who selected him in the third round (35th overall) of the 2015 draft, catching 67 passes for 661 yards and eight touchdowns.