Four years before the RNLI took over the station, two sisters named Martha and Margaret Llewellyn waded into the surf at Fishguard on 22 October 1846. The smack Margaret of Barmouth was breaking up offshore, and three men were drowning in water shallow enough to reach. The sisters did. They pulled all three out. The Royal National Institution awarded both of them silver medals in 1847, alongside John Acraman, the schooner master John Evans, William Jenkins, and William Rees, all silver medals for separate rescues in the same brief window of the 1840s. Six silver medals in less than a decade. The coast around Fishguard was a hard place to be a sailor.

On 7 December 1854 the RNLI's committee resolved to send a thirty-foot self-righting lifeboat of Mr Peake's new design to Fishguard, along with funds for a boathouse. A local committee chaired by the Reverend C. H. Barham of Trecwn had raised 193 pounds, enough to be formally accepted as a branch. The boat arrived in August 1855, carried first by the South Wales Railway and then the Great Western to Haverfordwest before being hauled overland to Fishguard. A No. 2 station opened in 1869 with a larger twelve-oared boat, funded by Captain Saumarez Fraser, RN, through a public appeal in Worcester, where the boat was paraded through the streets and named Fraser before being launched on demonstration in the River Severn. The big nights came. On 16 November 1882, the Fishguard lifeboat attended fifteen separate vessels in a single storm and saved 46 lives. In May 1874 the crew received 27 pounds for a single month's work that included rescuing 17 sailors from four different ships.

Twenty-eight medals have been awarded to Fishguard crewmen across two centuries: eighteen silver, nine bronze, and one gold. The gold went to Coxswain John Howells in 1921 for what became known as the Gold Medal Service. Three other crew members received silver that same year; nine others received bronze, a clean sweep of awards from a single rescue. In February 1946, the lifeboat White Star spent more than twenty-four hours at sea in severe weather standing by a broken-down submarine, helping rescue her crew. The dead are remembered in the station's roll of honour, the names of men who went out in the same boats and did not come back. Every lifeboat station in Britain keeps a list like this. Fishguard's is in the boathouse on the quay.

In November 1993 the BBC children's programme Blue Peter launched its Pieces of Eight appeal to fund six new inshore lifeboats around the British coast. Schoolchildren collected aluminium ring-pulls, raised over 1.4 million pounds, and overshot the target so dramatically that the RNLI was able to fund an all-weather boat as well. The new lifeboat arrived at Fishguard in 1994, a Trent-class designed for offshore work in heavy seas. On 17 June 1995, in front of a crowd that filled the breakwater, the Blue Peter presenters carried out the naming ceremony. The boat is 14-03 Blue Peter VII (ON 1198), and she is still on station. Beside her, the inshore lifeboat Edward Arthur Richardson has been on call since 2015. They go when the call comes.