A ship's surgeon, Wafer made several voyages to the South Seas and visited Maritime Southeast Asia in 1676. In 1679 he sailed again as a surgeon, soon after settling in Jamaica to practise his profession.
After being injured during an overland journey, Wafer was left behind with four others in the Isthmus of Darien in Panama, where he stayed with the Cuna Indians. He gathered information about their culture, including their shamanism and a short vocabulary of their language. He studied the natural history of the isthmus. The following year, Wafer left the Indians promising to return and marry the chief's sister and bring back dogs from England. He fooled the buccaneers at first as he was dressed as an Indian, wearing body-paint and ornamented with a nose-ring. It took them some time to recognise him.
By 1690 Wafer was back in England and in 1695 he published A New Voyage and Description of the Isthmus of America, which described his adventures. It was translated into French (1706), German (1759), and Swedish (1789).
He died in London in 1705.