Political activist
In politics Vaughan supported John Wilkes. He sent his five sons to Warrington Academy, Benjamin and William being taught by Joseph Priestley, with whom a strong family connection was forged. In early 1769 Vaughan was using his contact with John Seddon of Warrington to circulate Wilkite literature in Lancashire. He also hoped to recruit supporters in Manchester and Liverpool through Seddon. With Joseph Mawbey and others, Vaughan was a founder of the Bill of Rights Society (Society of Gentlemen Supporters of the Bill of Rights). It was a trust giving financial support to Wilkes, and the treasurers were Vaughan, Richard Oliver and John Trevanion (1740–1810). The Society set about dealing with Wilkes's tangled money affairs.
Vaughan belonged to what Benjamin Franklin fondly called the Club of Honest Whigs, which met at St Paul's Coffee House in the cathedral churchyard (see English coffeehouses in the 17th and 18th centuries). His support for the cause of Corsica in 1768 brought him the acquaintance of James Boswell through the Club. Vaughan was a trustee of funds for Corsica, with William Beckford and Barlow Trecothick.
In December 1774 Franklin and Josiah Quincy II stayed with Vaughan at Wanstead in Essex. In the period 1781–2 the parliamentary reformer Christopher Wyvill met radical leaders at Vaughan's house. There resulted a political pact for the following session of parliament, of mutual support between Wyvill and a radical group around Vaughan (including John Jebb, John Horne Tooke, and James Townsend). Vaughan joined the Society for Constitutional Information in the 1780s. Through William Beckford, he met the Earl of Shelburne. When Shelburne became Prime Minister, the Vaughan family influence reached foreign policy, trying to split the United States from their French allies in some ultimately unsuccessful moves of 1782.
The Vaughan family was part of the Newington Green congregation of the dissenting minister Richard Price. Samuel Vaughan was a friend of the elder William Hazlitt, the Unitarian minister. Vaughan's religious views have been described as "free-thinking Unitarian".