He was the son of George Carew, dean of Windsor. In 1574 he went to Ireland as a soldier and distinguished himself in 1577 in defending Leighlin Castle, County Carlow, from the Irish rebels. Well liked by Elizabeth and the powerful Cecil family, he was in 1586 knighted and made master of the ordnance in Ireland. He became lieutenant general of the ordnance in England in 1592, in which capacity he accompanied Robert Devereux, 2nd Earl of Essex, on the English naval raid on Cádiz, Spain, in 1596 and on the expedition to the Azores in 1597. In 1598 he attended Sir Robert Cecil, the ambassador, to France. He was appointed treasurer at war to Essex in Ireland in March 1599, and, on the latter's sudden departure in September of the same year, leaving the island in disorder, Carew was appointed a lord justice.

In 1600 Carew was appointed president of the province of Munster, where his military leadership and stern administrative measures contributed to the suppression of the Irish rebels under Hugh O'Neill, 2nd Earl of Tyrone, and won the admiration of Queen Elizabeth. In 1605, two years after Carew's return to England, King James I made him Baron Carew of Clopton. He was master of the ordnance from 1608 to 1617, and in 1618 he tried unsuccessfully to prevent the execution of his close friend Sir Walter Raleigh for treason. After the accession of Charles I in 1625, Carew was made Earl of Totnes (Feb. 5, 1626).

As an antiquary, Totnes collected many Irish historical and genealogical materials, from which Sir Thomas Stafford, who was probably his illegitimate son, compiled Pacata Hibernia (1633; “Pacified Ireland”), an account of the Irish rebellion. Totnes had a daughter but no legitimate male issue, and his titles became extinct upon his death.