On 10 January 1642 Parliament appointed him commander of the trained bands of London, 6,000 well equipped and trained men. That night Charles I fled London. Skippon was soon involved in an attempt to replace Sir John Byron as constable of the Tower of London, blockading the Tower with the trained bands, before making a failed attempt to storm the Tower while Byron was absent at Parliament. The importance of the Trained Bands was recognised on 10 May, when Skippon reviewed them in the presence of all of the leading members of Parliament.
This importance was amply demonstrated in the aftermath of Edgehill. Skippon and his trained bands were the only infantry in London, and with the earl of Essex and his cavalry they formed the basis of the Parliamentary army that on 13 November faced down the King at Turnham Green. At some point around this date Skippon was appointed Sergeant-major-general of Essex's army, and he remained with the field army for most of the rest of the war. He was thus present at the capture of Reading in April 1643, on Essex's march to relieve Gloucester, and on the march back towards London which ended in the First Battle of Newbury (20 September 1643). Key to the battlefield was control of a long ridge south of Newbury, and Skippon's role was to occupy the northern end of that ridge, known as 'Round Hill', which due to Royalist inactivity he was able to do before the battle started. Once the battle started, his position came under severe pressure, which he was able to relieve by bringing up the London trained bands, being held in reserve, and he was able to move up some heavy guns, which gained him control of that part of the field, although the battle ended without a clear result, and Charles marched off back to Oxford.
In 1644 Skippon was once again sergeant-major-general for Essex, this time on his disastrous march into Cornwall, which ended with defeat at Lostwithiel. The Battle of Castle Dore (31 August-1 September 1644) saw Essex slip away from his surrounded army, leaving Skippon to suffer the indignity of surrender, having to abandon all of his guns and ammunition, and march his men through the Royalist lines in front of the King. Although dramatic, this did not destroy this army, and by mid October Essex had re-equipped his infantry and had 4,000 foot at Portsmouth, which under Skippon marched to join the Parliamentary concentration around Newbury. The 2nd Battle of Newbury (27 October 1644) was very poorly managed by Parliament. Despite outnumbering the Royalists, Parliament did it's best to eliminate that advantage, vesting command in a committee of senior commanders, which when Essex became ill gave Manchester seniority, and left Skippon in charge of Essex's infantry. The committee decided that the Royalist position was too strong for a simple frontal attack, and sent Waller, with Essex's army, on a long march that would allow them to attack Charles from the rear. This plan required Manchester to attack at the same time as Waller, but when Waller's attack began at 3 p.m., with Skippon commanding the infantry, Manchester was not ready, and his attack did not come until 4, too late in the day for there to be an decision, and overnight Charles and his army escaped the trap.
The failure at Newbury was a key factor in the formation of the New Model Army. Skippon was the first senior officer to be decided, appointed major-general commanding the Foot unanimously, soon to be joined by Fairfax as commander, and Cromwell as lieutenant-general. Skippon also directly commanded a regiment of foot. It is a mark of his general popularity that Skippon was chosen to announce the new arrangements to the army (5 April 1645), there being some worry that at least some of the army would be unhappy with the change of commander.
Skippon thus found himself directing the arrangement of the infantry on the battlefield of Naseby (14 June 1645). He chose to follow the Swedish fashion, putting five regiments in the front line, with another three forming a second line staggered to cover the gaps in the first. His own regiment he placed at the far left of the first line. However, he was hit under the ribs by a musket ball in the first exchange of fire, and although he stayed on his horse, and on the battlefield, the news reduced the morale of the Parliamentary infantry, and the front line crumpled back into the second, only being rescued by the victory of Cromwell's cavalry, who were then free to attack the Royalist infantry.
Skippon remained important after Parliament's victory. He was in charge of the force which took custody of Charles I off the Scots and Newcastle on 30 January 1647. During the Second Civil War he was once again in London, and when the earl of Norwich captured Bow Bridge (3 June 1648), it was Skippon who ordered the gates of London closed against him. Once peace was secure, he served on the council of state, and on Cromwell's councils. When Cromwell appointed the Major-generals to rule the country for him, Skippon was appointed to command the London district, where his popularity was always high. He even retained his position under the restored Parliament in the build up to the Restoration, but soon after died.