A grandson of Edmund Calamy the Elder, he was born in the City of London, in the parish of St Mary Aldermanbury.

While there, he declined an offer of a professor's chair in the University of Edinburgh made to him by the principal, William Carstares, who had gone over on purpose to find suitable men for such posts.

After his return to England in 1691 he began to study divinity, and on Richard Baxter's advice went to Oxford, where he was much influenced by William Chillingworth.

He declined invitations from Andover and Bristol, and accepted one as assistant to Matthew Sylvester at Blackfriars, London (1692).

In 1702 he was chosen one of the lecturers in Salters' Hall, and in 1703 he succeeded Vincent Alsop as pastor of a large congregation in Tothill Street, Westminster.

In 1709 Calamy made a tour through Scotland, and had the degree of Doctor of Divinity conferred on him by the universities of Edinburgh, Aberdeen and Glasgow.

Accordingly, he composed an abridgment of it, with an account of many other ministers who were ejected in 1662 after the Restoration of Charles II; their apology, containing the grounds of their nonconformity and practice as to stated and occasional communion with the Church of England; and a continuation of their history until the year 1691.