Israel Pownoll launched her at Plymouth Dockyard on 31 March 1763, a Bellona-class third rate: 168 feet on the gundeck, 46 feet 9 inches in the beam, 1,603 tons burthen, seventy-four guns. The 74 was the workhorse of the sailing navy, heavy enough to stand in the line and fast enough to be useful, and the Bellonas were among the best of them. Her first war was the American Revolutionary War: the Channel Fleet, then the Battle of Cape St Vincent in 1780, then east in early 1782 with Commodore Sir Richard Bickerton's squadron of five ships — too late for that year's fighting in India, but in time for Cuddalore in 1783, the last battle of the war. She came home at the end of 1785 and was laid up through the peace.

The French Revolutionary Wars brought her out again under Captain James Gambier. At the Glorious First of June in 1794 she went in hard against Mucius and Tourville and was one of only two British ships completely dismasted in the battle. Repaired, she joined Admiral William Hotham in the Mediterranean in time for the Battle of Hyères that July, and in 1798, under Captain John Peyton, she was back there for the Nile. Then came the boat actions, the unglamorous and murderous work of cutting out enemy shipping. On 1 July 1800, in Bourneuf Bay, boats from Defence, Fisgard, Renown and the hired armed cutter Lord Nelson pulled in against a French convoy at the Île de Noirmoutier, destroying a 20-gun vessel, a lugger, two schooners and a cutter and burning some fifteen merchantmen loaded with corn for the fleet at Brest. Ninety-two of the 192 men who went in did not come back; they were taken prisoner when their boats grounded.

In 1801 she went to the Baltic under Captain Lord Henry Paulet with Hyde Parker's fleet and was present at Copenhagen, held in the reserve and never engaged. Four years later, off Cape Trafalgar under Captain George Johnstone Hope, she had a very different afternoon: she captured the Spanish San Ildefonso and fought the Berwick, losing 36 men killed and wounded. In 1809 she supported the Walcheren campaign, the disastrous attempt on Vlissingen and Antwerp that killed far more men by fever than by fighting. By 1811 she was a Baltic convoy escort in the Gunboat War against Denmark-Norway, and in November she joined the last homeward convoy of the year out of Hanöbukten — 129 merchant ships under Vice-Admiral James Saumarez in Victory, with Rear-Admiral Robert Carthew Reynolds flying his flag in the 98-gun St George.

St George had already been half-wrecked once. She had grounded at Rødsand in November, lost every mast and her rudder, and was crossing the North Sea on a jury rig with a makeshift rudder lashed on with chain. Defence and the 74-gun Cressy were detailed to stay with her. On 23 December a violent northwesterly caught them off the Jutland coast, and it became clear that all three were being set down onto a lee shore. Cressy hauled off and survived. Defence, under Captain David Atkins, tried to take St George in tow; the hawser parted. Then Atkins is said to have asked whether the admiral had signalled him leave to part company, and on being told no, answered: "I will never desert my Admiral in the hour of danger and distress." That version comes from Brenton's naval history of 1837, and it is the one that stuck. The Annual Register told it the other way round — Defence struck first, and St George, anchoring, swung on her cable and went ashore after her — and Gentleman's Magazine agreed. The accounts have never reconciled.

Defence grounded on 24 December 1811 and the sea broke her open. Of 597 men and boys, 583 died, Atkins among them; fourteen survived, and even that count varies between sources by a man or two. A few miles away St George was going to pieces with nearly 740 aboard — the two wrecks together put roughly 1,400 bodies on the beach over the following fortnight, along a strip of shore where almost nobody lived. Denmark was at war with Britain. The Danes buried the dead anyway, in the sand dunes at Thorsminde that have been called Dead Men's Dunes ever since, and gave Captain Atkins full military honours. Atkins had been at sea since boyhood: midshipman under Erasmus Gower in Edgar in 1780–81, third lieutenant in Lion, a navigator whose skill with lunar observations John Barrow thought remarkable in a young man. Whatever the truth of the signal, he was the one who stayed.