He was the eldest son of Sir Thomas Haselrig (alternative spellings "Hesilrige" and "Haselrigge"), 1st baronet (c. 1622), of Noseley, Leicestershire, a member of a very ancient family settled in Northumberland and Leicestershire, and of Frances, daughter of Sir William Gorges, of Alderton, Northamptonshire.
He early imbibed strong puritanical principles, and showed a special antagonism to Laud. He sat for Leicestershire in the Short and Long Parliaments in 1640, and took a principal part in Strafford's attainder, the Root and Branch Bill and the Militia Bill of 7 December 1641, and was impeached on 3 January 1642, along with John Hampden, Denzil Holles, John Pym and William Strode. He showed much activity in the Great Rebellion, raised a troop of horse for Essex, fought at Edgehill, commanded in the West under Waller, being nicknamed his fidus Achates, and distinguished himself at the head of his cuirassiers, the London lobsters at Lansdown on 5 July 1643, at Roundway Down on 13 July, at both of which battles he was wounded, and at Cheriton, 29 March 1644.
On the occasion of the breach between the army and the parliament, Haselrig supported the former, took Cromwell's part in his dispute with Manchester and Essex, and on the passing of the Self-denying Ordinance gave up his commission and became one of the leaders of the Independent party in parliament. On 30 December 1647 he was appointed governor of Newcastle, which he successfully defended, besides defeating the Royalists on 2 July 1648 and regaining Tynemouth. In October he accompanied Cromwell to Scotland, and gave him valuable support in the Scottish expedition in 1650.
Hesilrige, though he approved of the king's execution, had declined to act as judge on his trial. He was one of the leading men in the Commonwealth, but Cromwell's expulsion of the Long Parliament threw him into antagonism, and he opposed the Protectorate and refused to pay taxes. He was returned for Leicester to the parliaments of 1654, 1656 and 1659, but was excluded from the two former. He refused a seat in the Lords, whither Cromwell sought to relegate him, and succeeded in again obtaining admission to the House of Commons in January 1658.
On Cromwell's death Haselrig refused support to Richard, and was instrumental in effecting his downfall. He was now one of the most influential men in the council and in parliament. He attempted to maintain a republican parliamentary administration, "to keep the sword subservient to the civil magistrate," and opposed Lambert's schemes. On the latter succeeding in expelling the parliament, Haselrig turned to General George Monck for support, and assisted his movements by securing Portsmouth on 3 December 1659. He marched to London, and was appointed one of the council of state on 2 January 1660, and on 11 February a commissioner for the army. He was completely deceived by Monck, and trusting to his assurance of fidelity to the "Good Old Cause" consented to the retirement of his regiment from London. At the Restoration his life was saved by Monck's intervention, but he was imprisoned in the Tower.
Clarendon describes Haselrig as "an absurd, bold man." He was rash, "hare-brained," devoid of tact and had little claim to the title of a statesman, but his energy in the field and in parliament was often of great value to the parliamentary cause. He exposed himself to considerable obloquy by his exactions and appropriations of confiscated landed property though the accusation brought against him by John Lilburne was examined by a parliamentary committee and adjudged to be false.
Haselrig married (1) Frances, daughter of Thomas Elmes of Lilford, Northamptonshire, by whom he had two sons and two daughters, and (2) Dorothy, sister of Robert Greville 2nd Lord Brooke, by whom he had three sons and five daughters The family was represented in 1907 by his descendant Sir Arthur Grey Hazlerigg of Noseley, 13th Baronet.