Master Shipwright John Tippetts launched the Dartmouth at Portsmouth Dockyard on 22 September 1655. She was one of six fifth-rates ordered by the Commonwealth of England on 28 December 1654, all built in the state dockyards under the protectorate of Oliver Cromwell. The ship carried 22 guns, measured 80 feet on the keel, 24 feet in breadth, and 10 feet deep in hold. Her tonnage came to 260 by builder's old measurement. She cost £1,693 to build, or about £6 10s per ton. The name commemorated the capture of Dartmouth in Devon by Parliamentary forces under Thomas Fairfax in January 1646, an episode of the English Civil War still fresh in public memory. Tippetts had learned his trade in Denmark, where Dutch ship-building techniques were standard, and the archaeological evidence shows he used those Dutch methods to build the Dartmouth. She is the only known English example of such a ship.

In April 1666, during the Second Anglo-Dutch War, the Dartmouth captured three Dutch armed merchant ships off the coast of Ireland in company with a larger fourth-rate frigate and the 12-gun Little Gift. On 28 May 1672 she took part in the Battle of Solebay, the opening engagement of the Third Anglo-Dutch War. Between 1676 and 1677 she served in the Mediterranean under Rear Admiral John Narborough, hunting the Barbary corsairs who operated from Tripoli and Algiers. By 1689 she had been re-armed to carry 36 guns. On 1 May of that year she fought at the Battle of Bantry Bay, where 24 French warships covering the landing of supplies for Irish Jacobite forces clashed with 19 English ships. The French had the better of the engagement, badly damaging the English ships, but failed to press home their advantage. The Dartmouth survived again.

The most consequential moment of the Dartmouth's career came two months later. The town of Derry in northern Ireland was under siege by supporters of the deposed James II, defended by Irish Protestants supporting William III. Major-General Percy Kirke commanded a relief force sailing from Liverpool on 17 May 1689, with 24 transport ships carrying about 2,000 soldiers escorted by three warships: the Swallow, the Bonaventure, and the Dartmouth under Captain John Leake. The fleet arrived in Lough Foyle in early June. The river approach to Derry was defended by shore batteries and blocked by a heavy boom strung across the water. Kirke hesitated for weeks. Then, on the evening of 28 July, the attempt finally went in. The Dartmouth engaged the shore batteries, drawing their fire. The armed merchantman Mountjoy charged the boom and rammed it. The boom broke. The Mountjoy and another merchant, the Phoenix, forced their way through. The siege was relieved. The history of Ireland would be different had the Dartmouth not been there to take the cannon fire.

The storm in the Sound of Mull on 9 October 1690 ended the Dartmouth's career on rocks she could not have anticipated. The site lay undisturbed for 283 years. In 1973 divers from Bristol discovered the wreck on the north coast of Eilean Rudha an Ridire, a small island in the Sound. A recovered brass ship's bell confirmed the identification. Three years of archaeological survey followed. Twenty iron guns were identified. Parts of the hull were recovered for examination. The team brought up a varied collection of seventeenth-century military, navigational, medical, and domestic items, the everyday tools of a working warship. The Dutch shipbuilding methods Tippetts had used, never replicated in another English ship, were studied in detail. On 11 April 1974 the wrecksite was among the first designated under the Protection of Wrecks Act. It was redesignated in 1992 and became a Historic Marine Protected Area in 2013. The ship that helped relieve Derry remains, in fragments, beneath the Sound of Mull.