Indy also placed starting fullback Stanley Havili on the physically unable to perform list.
The moves come one day after Indy released 11 players. After Thursday's preseason finale at Cincinnati, all NFL teams must trim rosters to 53 by Saturday.
Ballard has a torn left Achilles' tendon and was expected to miss the entire season. John injured his lower right leg in the preseason opener and also was expected to miss a significant amount of time. Karim rejoined the Colts on Aug. 18 but the team has not disclosed his injury.
Havili has not practiced since starting camp on the PUP list.