Mahomet was the great-grandson of Uncas, an important sachem of the Mohegan tribe. In 1735, Captain John Mason, a descendant of the settler who had been asked by Uncas to act as guardians and trustees over the Mohegan land, engineered Mahomet's election to the position of Sachem in place of his great Uncle, Ben Uncas, who was more favoured by the Colony of Connecticut.

By 1735, the Mohegan people had lost much of their planting and hunting lands to white settlers in New England. Accompanied by two settlers who supported his cause, John and Samuel Mason, and another Mohegan, AughQuant, Weyonomon travelled to England,^[1] where the trio rented accommodation at St Mary Aldermanbury in the City of London while they prepared their petition to the King. The King referred the matter to the Lords Commissioners on Foreign Trade and Plantations; however, both John Mason and Weyonomon succumbed to smallpox in 1736 before their case could be heard by the commission.^[2]

As a foreigner, he was not permitted to be buried in the City of London, and he was interred in an unmarked grave^[1] outside St Mary Overie, now Southwark Cathedral. On 22 November 2006, Queen Elizabeth II dedicated a memorial (a sculpture by British artist Peter Randall-Page) to Mahomet Weyonomon at the cathedral,^[3] accompanied by a traditional funeral ceremony conducted by members of the Mohegan tribe.^[1]

• Caulkins, Frances Manwaring. History of Norwich, Connecticut: from its possession by the Indians, to the year 1866. Self-published, 1866. 269.