[1][4] General Greene had been designed specifically for prohibition enforcement service and assumed Rum Patrol duty 15 May 1927 with a home-port of Boston, Massachusetts[4] Her routine consisted of picketing liquor laden "mother ships" and preventing them from offloading prohibited cargo to smaller contact boats that were used to deliver liquor to shore.

[4] With the end of prohibition in 1933, General Greene assumed a more traditional role of a Coast Guard cutter, that of search and rescue, law enforcement, merchant vessel inspection, and defense training.

On 25 May 1942 she engaged a German U-boat with depth charges in a dense fog off Nantucket Shoals while rescuing survivors from the British freighter SS Peisander.

[1] While attempting to assist a tug in distress, General Greene was swept ashore on Spring Hill Beach at East Sandwich, Massachusetts, by hurricane-force winds and 40-foot (12 m) waves on 4 March 1960.

[7][8] After her decommissioning, General Greene was transferred to Newburyport, Massachusetts, for use as a museum ship, but she was returned to the Coast Guard in 1976 and sold.