The move comes two weeks to the day after selecting running back Saquon Barkley with the No. 2 overall pick in the NFL draft.
Perkins, 23, suffered a pectoral muscle injury, which one source believed was a tear, before the start of the Giants' offseason workout program. He underwent a procedure recently and was waived with a non-football injury designation.
Pectoral tears are generally six-month injuries. That would put a good chunk of this season in doubt for Perkins. He's likely to go unclaimed given the injury, and could land on the reserve/NFI list. That would end his season.
The Giants have Barkley, Wayne Gallman and recently signed Jonathan Stewart in their backfield. Perkins was likely going to have to fight for his roster spot regardless. Gallman passed him on the depth chart midway through last season.
Perkins started the Giants' first four games in 2017 but finished with just 90 yards on 41 carries (2.2 yards per carry). He did not reach the end zone after a promising rookie season where he finished with 456 yards on 112 carries (4.1 YPC).
Orleans Darkwa, who remains unsigned, finished last year as the Giants' leading rusher with 751 yards rushing. Perkins ended the season as a third-string option. He had just nine carries over the final 13 weeks of the season.
The Giants drafted Perkins in the fifth round of the 2016 draft. He led the Pac-12 in rushing as a sophomore and rushed for over 1,300 yards as a junior.