Following shakedown off Florida's Cape Kennedy, James Monroe spent the early months of 1964 in ballistic missile tests.

On 17 January 1967, James Monroe completed her twelfth deterrent patrol, having operated from both Holy Loch, Scotland, and Rota, Spain.

Four days later, USS James Monroe entered Kings Bay and moored alongside Simon Lake's starboard side to begin a routine refit in preparation for another nuclear weapons deterrence patrol.

James Monroe was decommissioned on 25 September 1990 and stricken from the Naval Vessel Register the same day.

Ex-James Monroe entered the Nuclear Powered Ship and Submarine Recycling Program in Bremerton, Washington.