The younger son of Joseph (a clergyman) and Isabel, Langhorne was born at Winton near Kirkby Stephen. According to the parish register, "Joseph LANGHORN & Isabell BLAND of Winton" married "5 Aug 1718" Their church monument states:

1762. To. m. the Reverend Joseph Langhorne of Winton and Isabel his wife.

Her, who to teach this trembling hand to write,

Toil'd the long day, and watch'd the tedious night,

I mourn, tho' number'd with the heavenly host;

With her the means of gratitude are lost.

:—John Langhorne."

He was educated first in Winton, and later in Appleby. Following his 18th birthday, he became tutor to a Ripon family, and was later an Usher at the free school in Wakefield. In Wakefield he took orders, being ordained Deacon.

He was for two years a curate in London, and from 1766 Rector of Blagdon, Somerset, and later Prebendary of Wells.

He is chiefly remembered as being the translator, jointly with his brother, Rev. William Langhorne (1721—1772), of Plutarch's Lives, but in his day he had some reputation as a poet, his chief work in poetry being Studley Park and Fables of Flora. In his Country Justice (1774–77) he foreshadows George Crabbe, as in his descriptive poems he foreshadows William Wordsworth. He was twice married, and both of his wives died in giving birth to a first child. After the death of his first wife, Ann, in 1768, Langhorne went to live with his brother in Folkestone where William was perpetual curate and it was during this time they produced their translation. Langhorne remarried in 1772, and after visiting France and Flanders, returned to Blagdon.