He was born in London. His father, John Frere, a gentleman of a good Suffolk family, had been educated at Caius College, Cambridge, and would have been senior wrangler in 1763 but for the redoubtable competition of William Paley; his mother, daughter of John Hookham, a rich London merchant, was cultured and wrote verse in private. His father's sister Eleanor, who married Sir John Fenn (1739-1794), editor of the Paston Letters, wrote educational works for children under the pseudonyms "Mrs Lovechild" and "Mrs Teachwell". Young Frere was sent to Eton College in 1785, and there began an intimacy with George Canning which greatly affected his after life. From Eton, he went to his father's college at Cambridge, and graduated BA in 1792 and MA, in 1795. He entered public service in the foreign office under Lord Grenville, and sat from 1796 to 1802 as member of parliament for the close borough of West Looe in Cornwall.
From his boyhood he had been a warm admirer of William Pitt the Younger, and along with Canning he entered heart and soul into the defence of his government, and contributed freely to the pages of the Anti-Jacobin, edited by Gifford. He contributed, in collaboration with Canning, The Loves of the Triangles, a clever parody of Erasmus Darwin's Loves of the Plants, The Needy Knife-Grinder and The Rovers. On Canning's removal to the board of trade in 1809 he succeeded him as under-secretary of state; in October 1800 he was appointed envoy extraordinary and plenipotentiary to Lisbon; and in September 1802 he was transferred to Madrid, where he remained for two years. He was recalled on account of a personal disagreement he had with the duke of Alcudia, but the ministry showed its approval of his action by a pension of £700 a year.
He was made a member of the privy council in 1805; in 1807 he was appointed plenipotentiary at Berlin, but the mission was abandoned, and Frere was again sent to Spain in 1808 as plenipotentiary to the Central Junta. The condition of Spain rendered his position responsible and difficult. When Napoleon began to advance on Madrid it became a matter of supreme importance to decide whether Sir John Moore, who was then in the north of Spain, should endeavour to anticipate the occupation of the capital or merely make good his retreat, and if he did retreat whether he should do so by Portugal or by Galicia. Frere was strongly of opinion that the bolder was the better course, and he urged his views on Sir John Moore with an urgent and fearless persistency that on one occasion at least overstepped the limits of his commission. After the disastrous retreat to A Coruña, the public accused Frere of having endangered the British army, and though no direct censure was passed upon his conduct by the government, he was recalled, and the marquess of Wellesley was appointed in his place.
Thus ended Frere's public life. He afterwards refused to undertake an embassy to St Petersburg, and twice declined a peerage. In 1816 he married Elizabeth Jemima, dowager countess of Erroll, and in 1820, on account of her failing health, he went with her to the Mediterranean. There he finally settled in Malta, and though he afterwards visited England more than once, the rest of his life was for the most part spent in the island of his choice. In quiet retirement he devoted himself to literature, studied his favorite Greek authors, and taught himself Hebrew and Maltese. He welcomed English guests, and was popular with his Maltese neighbors. He died at Villa Frere in Pieta` close to Valletta.
Frere's literary reputation now rests entirely upon his spirited verse translations of Aristophanes, which remain in many ways unrivalled. The principles according to which he conducted his task were elucidated in an article on Mitchell's Aristophanes, which he contributed to The Quarterly Review, vol. xxiii. The translations of The Acharnians, The Knights, The Birds, and The Frogs were privately printed, and were first brought into general notice by George Cornewall Lewis in the Classical Museum for 1847. They were followed some time after by Theognis Restilutus, or the personal history of the poet Theognis of Megara, reduced from an analysis of his existing fragments. In 1817 he published a mock-heroic Arthurian poem entitled Prospectus and Specimen of an intended National Work, by William and Robert Whistlecraft, of Stowmarket in Suffolk, Harness and Collar Makers, intended to comprise the most interesting particulars relating to King Arthur and his Round Table. William Tennant in Anster Fair had used the ottava rima as a vehicle for semi-burlesque poetry five years earlier, but Frere's experiment is interesting because Byron borrowed from it the measure that he brought to perfection in Don Juan.
Frere's complete works were published in 1871, with a memoir by his nephews, WE and Sir Henry Bartle Frere, and reached a second edition in 1874.