Britannia was first commissioned in August 1778, under the command of Captain Charles Morice Pole, for the American Revolutionary War.

Britannia was coppered at Portsmouth Dockyard in January 1780, and in September Captain James Bradby assumed command.

Vice-Admiral Charles Thompson took Britannia as his flagship early in 1797, and as such the ship fought at the Battle of Cape St. Vincent on 14 February, in which she had one man wounded.

With the Napoleonic Wars having begun, the ship was then recommissioned by Captain Lord Northesk in April 1803 to serve on the Brest blockade.

In April 1804 Northesk was promoted to rear-admiral, and Britannia became his flagship with Captain Charles Bullen assuming command in June.

On 21 October 1805 Britannia fought in the windward column of the British fleet at the Battle of Trafalgar, in which she had ten men killed and a further forty-two wounded.

In March she was recommissioned under the command of Captain James Nash, becoming the flagship of Admiral Sir John Duckworth, Commander-in-Chief, Plymouth.