Through strong family influence and the recommendation of Walpole he was cbosen in 1721 a lord of the Treasury. The following year he was returned for Sussex county. In 1724 he entered the ministry as secretary of war, but this office he exchanged in 1730 for the more lucrative one of paymaster of the forces. He made himself conspicuous by his support of Walpole on the question of the excise, and in 1743 a union of parties resulted in the formation of an administration in which Pelham was prime minister, with the office of Chancellor of the Exchequer; but rank and influence made his brother, the duke of Newcastle, very powerful in the cabinet, and, in spite of a genuine attachment, there were occasional disputes between them, which led to difficulties.
Being strongly in favour of peace, Pelham carried on the War of the Austrian Succession with languor and indifferent success, but the country, wearied of the interminable struggle, was disposed to acquiesce in his foreign policy almost without a murmur. King George II, thwarted in his own favourite schemes, made overtures in 1746 to Lord Bath, but his purpose was upset by the resignation of the two Pelhams (Henry and Newcastle), who, however, at the king's request, resumed office. Pelham remained prime minister till his death, when his brother succeeded him.
His very defects were among the chief elements of Pelham's success, for one with a strong personality, moderate self-respect, or high conceptions of statesmanship could not have restrained the discordant elements of the cabinet for any length of time. Moreover, he possessed tact and a thorough acquaintance with the forms of the House of Commons. Whatever quarrels or insubordination might exist within the cabinet, they never broke out into open revolt. Nor can a high degree of praise be denied to his financial policy, especially his plans for the reduction of the national debt and the simplification and consolidation of its different branches.