In August 1642, Astley joined King Charles at Nottingham. He was dramatically appointed commander of the Royalist infantry when the Earl of Lindsey stepped down on the morning of the battle of Edgehill. Astley continued as commander of the Royalist foot throughout the First Civil War, participating in all the major battles fought by the King's Oxford army. He was one of the most disciplined and stalwart of the Royalist generals, but he was not a strong presence on the King's Council of War and took no part in court politics. In recognition of his services, he was created Baron Astley of Reading in November 1644. At the fateful battle of Naseby in June 1645, Astley's infantry came close to breaking Skippon's Parliamentarians in the centre, but were themselves routed after a decisive flank attack by Cromwell's Ironsides.
After the defeat of Naseby, the King removed the unpopular Charles Gerard from command of Royalist forces in Wales and appointed Astley in his place. Astley organised the chaotic administration of Royalist garrisons in the region and raised a force of 3,000 horse and foot in Worcestershire. This represented the last Royalist field army of the First Civil War. In March 1646, Astley set out from Worcester intending to march his troops to the King's headquarters at Oxford but he was intercepted and defeated at Stow-on-the-Wold by a superior Parliamentarian force and obliged to surrender. Astley was imprisoned in Warwick Castle until the surrender of Oxford in June 1646.