Carew was reprimanded for the vigour of his response to the 1549 Prayer Book Rebellion, the rising in Devon and Cornwall occasioned by the issue of the reformed Book of Common Prayer. In 1553, he proclaimed Queen Mary I of England in the west. However, at the end of the year he conspired (as part of "Wyatt's Rebellion") against her proposed marriage to Crown Prince Philip II of Spain: unlike many of his co-conspirators, he managed to escape arrest, and fled into exile on the European mainland in January 1554. In May 1556 he was arrested with Sir John Cheke in Flanders and returned unceremoniously to England in a fishing boat. He was held in the Tower of London until October 1556, his release being secured on payment of certain family debts due to the Crown.