During the Civil War he declared for Parliament and served in the Earl of Manchester's army. He fought in many of the major battles of the war and joined the New Model Army in 1645. By the end of the conflict he had risen to the rank of major-general and was a noted friend and supporter of Oliver Cromwell. He was elected to the Long Parliament for Wendover in 1646. His regiment maintained strong Leveller sympathies, mutinying in 1647.
When conflict resumed he was wounded at Appleby in July 1648. He had to return to London but was well enough to command the escort that brought the King to London in January 1649. Harrison sat as a commissioner at the trial and was the seventeenth of fifty-nine commissioners to sign the death warrant of King Charles I. In 1650, Harrison was appointed to a military command in Wales where he was apparently extremely severe. He was promoted to the rank of Major-General in 1651 and commanded the army in England during. He fought at the battle of Knutsford in August and at Worcesterin September 1651. By the early 1650s Harrison was associated with the radical Fifth Monarchists and became one of their key speakers. He still supported Cromwell and aided in the dissolution of the Rump Parliament in April 1653. He opposed the parliament on the basis that it was blocking more stringent religious reforms – he wanted a more 'godly' parliament. Harrison was a radical member of the Nominated Assembly that replaced Parliament. When the assembly was dissolved, Harrison and others refused to leave and had to be forced out by soldiers. Harrison was dismissed from the Army in December. Like many, he was outraged by the formation of the Protectorate and the elevation of Cromwell to Lord Protector. Under the Protectorate Harrison was imprisoned four times.
Arrest and trial
After Cromwell's death Harrison remained quietly in his home, supporting none of the contenders for power. Following the Restoration, Harrison declined to flee and was arrested in May 1660. He was tried on 11 October 1660. Edmond Ludlow described the trial in his memoirs,
Execution
Major-General Harrison was the first of the Regicides to be executed by being hanged, drawn and quartered on 13 October 1660. Harrison, after being hanged for several minutes and then cut open, was reported to have leaned across and hit his executioner—resulting in the swift removal of his head. His entrails were thrown onto a nearby fire. Samuel Pepys wrote an eyewitness account of the execution at Charing Cross, in which Major General Harrison was drily reported to be "looking as cheerful as any man could do in that condition". This account is also quoted on a plaque on the wall of the Hung, Drawn and Quartered public house near Pepys Street, where the diarist lived and worked in the Navy Office. In his final moments, as he was being led up the scaffold, the hangman asked for his forgiveness. Upon hearing his request Thomas Harrison replied, "I do forgive thee with all my heart... Alas poor man, thou doith it ignorantly, the Lord grant that this sin may be not laid to thy charge." Thomas Harrison then gave all of the money that remained in his pockets to his executioner and was thereafter executed. Edmond Ludlow also provided an account of the execution at Charing Cross, "the sentence which had been pronounced in consequence of the verdict was executed upon Major-General Harrison at the place where Charing Cross formerly stood, that the King might have the pleasure of the spectacle, and inure himself to blood. According to Ludlow, "On the fifteenth, Mr. John Carew suffered there also, even their enemies confessing that more steadiness of mind, more contempt of death, and more magnanimity could not be expressed. To all who were present with them either in prison or at the place where the sentence was executed, they owned that having engaged in the cause of God and their country, they were not at all ashamed to suffer in the manner their enemies thought fit, openly avowing the inward satisfaction of their minds when they reflected upon the actions for which they had been condemned, not doubting the revival of the same cause; and that a time should come when men would have better thoughts of their persons and proceedings."
