Paul Sinha was born in Luton, Bedfordshire, to Indian parents of Bengali Hindu origin. He was educated at Dulwich College and St George's Hospital Medical School. He is a former general practitioner, qualifying in 1995. While at medical school he developed a taste for the stage in St George's annual revue and refined his comedy as co-editor of the medical school newsletter, popularly known as the Slag Mag.
Paul began performing stand-up while working as a junior doctor in hospitals in London and King's Lynn. His early material drew on his sexuality and ethnicity, with heavy use of puns. He promoted himself as "the world's only gay Anglo-Bengali GP turned stand up comedian". In 1999, he came third in the final of the Hackney Empire New Act of the Year.
After several years of combining touring with his nascent medical career, Sinha's breakthrough came with his second solo Edinburgh show, Saint or Sinha?, which earned him an if.comeddie nomination in 2006.