He piloted Gemini 9 in June 1966, piloted Apollo 10, orbiting the Moon in May 1969, and commanded Apollo 17 in December 1972. He was the second US astronaut to walk in space and the last person to walk on the Moon, having been one of two astronauts to fly there twice (the other being James Lovell).

Cernan and Jack Schmitt stayed on the lunar surface for three days, setting a record for the longest lunar surface extravehicular activity (22 hours and 6 minutes). Cernan logged more than 566 hours in space, including more than 73 hours on the Moon. He was selected as an astronaut in 1963 and resigned from NASA in 1976. In 2016, Cernan appeared in the British documentary The Last Man on the Moon. In 1999 he published his memoir The Last Man on the Moon (with co-author Donald A. Davis). He died in Houston on 16 January 2017.