In 1772, Southampton – at the time commanded by the capable John MacBride, destined for a distinguished naval career – was sent to Elsinore, Denmark, to take on board and convey to exile in Germany the British Princess Caroline Matilda, George III's sister, who had been deposed from her position as Queen of Denmark due to her affair with the social reformer Johan Struensee.

[3] On 3 August 1780, Southampton captured the French privateer lugger Comte de Maurepas, of 12 guns and 80 men, under the command of Joseph Le Cluck.

Gorgon, Courageux, and the hired armed cutter Fox were in company at the time,[8] and with the British fleet outside Toulon.

She was engaged on two cruises of observation in the chops of the Channel and a voyage to Gibraltar conveying Prince Edward to his new command.

Southampton was readied as part of Lord Howe's fleet to respond to the Nootka sound incident, but was not required to put to sea.

Keats had written to the Admiralty concerned at the state of his new command, which had not been in the docks for three years, during which she had grounded several times, and in 1790 she was paid off.

[13] Lloyd's List reported that Southampton and the sloop-of-war HMS Brazen had run aground and lost their masts on the coast of Mississippi during a great hurricane on 19 and 20 August 1812, but that the crews were saved.

On 22 November, Southampton, under the command of Captain James Lucas Yeo, captured the American brig USS Vixen.

Vixen was armed with twelve 18-pounder carronades and two 9-pounder bow chasers, and had a crew of 130 men under the command of Captain George Reed.