After studying at Oxford University and the Middle Temple, London, Hopton served in the army of the Elector Palatine in the early campaigns of the Thirty Years' War (1618–48), and in 1624 he entered the House of Commons. As a Puritan, he initially supported Parliament in its conflict with the king. But when Parliament went so far as to claim control over the armed forces (1642), Hopton changed sides and became an ardent Royalist. With the outbreak of the Civil War, the king made him a lieutenant general for western England. Hopton won a brilliant victory at Stratton, Cornwall, in May 1643, and in June he overran the neighbouring county of Devon. He was badly wounded, however, while inflicting a defeat on Sir William Waller at Lansdown, Somerset, on July 5. Waller then had him surrounded at Devizes until Royalist reinforcements broke the siege on July 13.

In September 1643 Hopton was made Baron Hopton of Stratton, but by the time he succeeded to the command of the Royalist army early in 1646, it was no longer possible to prevent the Parliamentary victory. After one last, futile stand at Torrington, Devon, he surrendered to General Thomas Fairfax on March 14, 1646. He tried unsuccessfully to hold the Scilly Isles off Cornwall for the Royalists and then retired into exile. Hopton's marriage resulted in no children, and the barony became extinct.