Hoadly was born 30 September 1643 at Guildford, New England, whither his parents had fled at the outbreak of the great rebellion.
In 1655 his parents returned to Great Britain and settled in Edinburgh, where Samuel was educated, matriculating in 1659 in the university.
He was twice married; first in 1666 to Mary Wood, who died in childbirth in 1668; secondly, in 1669, to Martha, daughter of a priest called Pickering.
Hoadly's Natural Method of Teaching, being the Accidence in Questions and Answers &c., a kind of English and Latin grammar combined (1683), was the most popular school manual of the age, and before 1773 reached its eleventh edition.
It was probably owing to the recommendation of Grævius that several young foreign scholars became boarders in Hoadly's house in order to learn English.