In 1866 his wife was Margaret Wright Sheraton. She died in 1874. And in 1875 Sheraton remarried. His new wife was Rachel Mary Sheraton. At this time he was rector of the parish at Pictou, Nova Scotia. Sheraton spent 13 years in parochial work. In 1877 James P. Sheraton moved to Toronto to become the new principal of the Protestant Episcopal Divinity School, later named Wycliffe College. In 1883 Sheraton received a Doctor of Divinity from Queen’s University and in 1886 he received a Doctor of Laws from the University of Toronto.
It was under Sheraton that Wycliffe College began to grow. Under his leadership the College found its new home at College Street and later at Hoskin Avenue. While principal Sheraton was on the Board of Examiners for Divinity Degrees. He was also a member of the Senate of the University of Toronto. Sheraton retained the position of principal until his death in 1906.