On 21 October 1805 "Agamemnon" fought in the Battle of Trafalgar. "Agamemnon" was positioned eighth in Nelson's weather column, with ahead and astern. Once engaged, she was firing both batteries, eventually pounding the great Spanish four-decker "Santísima Trinidad" until that ship was dismasted and, with 216 of her complement dead, struck her colours. Before Berry could take possession of the prize, the enemy van division began bearing down on the British line, having previously been cut off from the battle by Nelson's line-breaking tactics. With Nelson already dying below decks on "Victory", Captain of the Fleet Thomas Hardy ordered "Agamemnon" and several other ships to intercept them. Three of the enemy ships broke off and ran for Cádiz; after briefly engaging "Intrépide" the British ships moved to try to cut off the fleeing ships. Over the course of the battle, "Agamemnon" suffered just two fatalities, and eight men were wounded.