Blake joined the Parliamentary Army of Sir John Horner and became a captain in Alexander Popham's regiment. At the defence of Bristol in 1643, he earned a reputation as a determined fighter. He fought on after the parliamentary commander Fiennes had surrendered the city and Prince Rupert, the Royalist commander, was minded to hang him. Promoted to Lieutenant Colonel, he was sent to defend Lyme against the royalist army of Prince Maurice. Though not the senior officer, it was Blake who directed the stubborn defence of the town, which saw off far superior numbers.
Blake moved on to Taunton in the late spring of 1644 to raise a new regiment for parliament. The new regiment, in turn, was despatched to join the army of the Earl of Essex, leaving Blake as Governor of the town with a makeshift force of 1,000. Between October 1644 and July 1645, Taunton endured three sieges, successively blockaded by Edmund Wyndham, Governor of Bridgwater, Sir John Berkley and Lord Goring.
By the end of his heroic defence of Taunton, the town, with the exception of the castle, was all but destroyed and the people starving - but the news had made Blake a hero in London. In November 1645, Blake went on to besiege and capture the last Royalist stronghold in Somerset, Dunster Castle, which surrendered in April 1646.
By the end of the First Civil War Blake was an established figure in the new hierarchy. Governor of Taunton, again MP for Bridgwater, his name appears in both parliamentary and county committees of the time. Staunchly anti-royalist, he was nevertheless a man of conservative social and religious views - typical of the Presbyterian establishment of the time. The growing differences between the army and parliament were an embarrassment to him. He took no part in the trial and execution of the King in January 1649.