Although his brother Henry stood for and won election, Thomas took his position just after his 21st birthday, in the House of Lords, due to his granted title as the Duke of Newcastle. He was the only Prime Minister to have never sat in the House of Commons. The Hollis was added to his last name as required by his uncle, John Hollis, under the terms of his will which left Thomas with a large estate and income. This property and money enabled him to influence and direct over a dozen constituencies and hence their choices for Parliament. This gave Pelham a base in the House of Commons from which the Whigs were to build a strong party alliance which helped them to gain power and use it, even against the King's wishes. His marriage to Lady Harriet Godolphin, in 1717, who was the Duke of Marlborough's

  daughter, elevated him into the highest circles of power in England. He became a member of the Privy Council in 1717 and one of the 13 Lord Justices who oversaw the running of Government for King George I when he returned to his real homeland Hanover. Thomas was joined in Parliament by his brother Henry who was elected to the House of Commons and by 1743 succeeded Walpole as Prime Minister.

In 1754 Henry Pelham died and Thomas Pelham-Hollis became Prime Minister in his place.  Thomas tried to persuade William Pitt to join him in preparations for an anticipated conflict with France which was to explode into the 7 years war. This war which was the first of truly global proportions rocked his ministry and he was unable to maintain the support of his followers and was forced to resign. His departure from centre stage was not a long one.

The Duke of Devonshire who had replaced him found that he could muster even less support and with Pitt finally as an ally he once again took the reins of the Prime Ministership. Pelham gave Pitt the responsibility for the execution of the war which was carried out brilliantly and lead to great victories in America and India. As the war was winding down King George II died and George II came to power with the intend of curbing the powers of Pelham and the Whigs. George did this by backing the Earl of Bute as an alternative to Newcastle. By 1762 Pelham (Newcastle) had had enough and stepped aside so that Bute could become Prime Minister. King George III forced the resignation of the Duke of Deveonshire because he was still supporting Pelham.

As his brother had done decades before Pelham asked his allies to resign on mass form government in order to force Bute's fall and George III's recognition of the power of Parliament. This time however, George worked closely with Bute in not only accepting the resignations but in also purging all remaining friends and allies of Pelham's from power. This fight in October of 1762 was known as the MASSACRE OF THE PELHAM INNOCENTS.

Newcastle continued to lose power through the death of his allies and the independent growth of his protégés. They saw power fleeing him and they too fled. He did however entry into the halls of power one last time in July 1765 when he was appointed Lord Privy Seal by his former support Rockingham, but was largely left out of the process of welding power. By 1768 suffering and incapacitated Newcastel passed away at his home in Claremont, Surrey.