They carried the Regulus I and Regulus II nuclear cruise missiles, deployed 1957–64, that were rapidly phased out by Polaris Submarine Launched Ballistic Missiles (SLBMs).

They and USS Halibut were the sole submarines designed specifically to carry Regulus missiles, and the only submarines capable of carrying Regulus II.

[4][2] Torpedo armament was the same as the Tangs, with six bow and two stern tubes.

The stern tubes were for "swim-out" weapons only, such as the Mark 37 ASW homing torpedo.

In Grayback's later role as an amphibious transport submarine, the former missile hangars were used to store SEAL Swimmer Delivery Vehicles and other equipment used by the SEALs and Marine Force Recon units.