Upon the Restoration in 1660, the new authorities deprived Wilkins of the position given him by Cromwell; he gained appointment as prebendary of York and rector of Cranford, Middlesex. In 1661, he was reduced to preacher at Gray's Inn, lodging with his friend Seth Ward. In 1662, he became vicar of St Lawrence Jewry, London. He suffered in the Great Fire of London, losing his vicarage, library and scientific instruments.