Early in the war, Sir Hugh Cholmley held Scarborough for Parliament. The castle on its precipitous headland, the strategic supply port below, the access to the coal trade out of the Tyne - it was a position Parliament needed to keep. In March 1643, Cholmley changed sides. His own cousin, Captain Browne Bushell, briefly seized the castle while Cholmley was away at York, but Cholmley persuaded Bushell to give it back. He refortified it for the King, building the South Steel Battery as an artillery position covering the harbour. For the next year, his small force was the only Royalist presence in east and north Yorkshire, but it raided as far as Beverley and Whitby, and the port became a haven for Royalist pirates harassing the colliers running coal to London. Parliament eventually decided that Scarborough mattered.

On 2 July 1644, the Parliamentarians and their new Scottish allies, the Covenanters, broke the Royalist army of the north at Marston Moor outside York. The next day, the Marquess of Newcastle - the King's captain-general in the north - boarded a ship at Scarborough with his senior officers and went into exile on the Continent. York surrendered two weeks later. Scarborough was suddenly the most important Royalist garrison in the whole north, and the most isolated. Cholmley's garrison began to desert; the castle fell into disrepair. In August, Lord Fairfax's army reached the edge of the town. Cholmley opened surrender negotiations purely to buy time. The negotiations dragged on, the surrender never happened, and Cholmley used the months to upgrade his defences for the real siege he knew was coming.

Sir John Meldrum took the town in February 1645 with almost no casualties on his side. Cutting off the Royalists from land and sea, he settled in to bombard the castle. Then, on 24 March, he was knocked off the cliff. Cholmley wrote afterwards that Meldrum had been trying to retrieve his hat from the wind. The more likely explanation, the chronicler noted dryly, is that a sudden gust simply blew the man off the edge. He survived, somehow, but the siege was delayed six weeks while he recovered. Meanwhile the Royalists drew water from the Well of Our Lady near the cliff edge and from a few local springs, ate their stockpiled food, and waited. When Meldrum resumed command in May, he set up the Cannon Royal - the largest gun in the country - inside the twelfth-century St. Mary's Church below the castle, and started firing 56-pound cannonballs at the keep.

The Cannon Royal pounded the castle keep for three days. The west wall collapsed, taking the roof and the floors with it. St. Mary's Church, the gun's firing platform, sustained terrible damage from the recoil and from Royalist counter-battery fire; one side of the church remains a ruin to this day. Cholmley's troops were credited with the destruction, though most of it was probably done by the Cannon Royal's own shock. The keep's collapse should have ended the siege. Instead it produced a strange consequence: the rubble filled the barbican entrance and cut the defenders off from their own gateway. Meldrum failed to realise this in time. On the night of 10 May the Royalists raided his artillery position, destroying it. The next day saw particularly bloody hand-to-hand fighting around the barbican, where neither side took prisoners and Meldrum himself was mortally wounded.

Sir Matthew Boynton replaced Meldrum and chose a different strategy: pure bombardment from land and sea, no more infantry assaults. The defenders ran out of water when the spring failed, ran low on gunpowder, suffered scurvy from their starving diet, and finally surrendered at noon on 25 July 1645. Of the original five hundred defenders, fewer than half came out alive, and only twenty-five were fit to fight. Cholmley received unusually generous terms - perhaps to end the bloodshed quickly - and left for exile in Holland. The castle was repaired and rearmed for Parliament. Three years later, when its new garrison went unpaid, they declared for the King again and a second, shorter siege began. The castle changed hands seven times between 1642 and 1648. Most of the keep is still missing. The standing shell on the cliff is what 1645 left behind.