He was the commander of Apollo 17 which went to the Moon in December 1972, joining a select band of American astronauts.
Mr Cernan was the 11th person to walk on the surface of the Moon when he stepped from the lunar module Challenger.
His lunar module pilot, Jack Schmitt, became the 12th, but as commander, Mr Cernan was the last to re-enter the Challenger, so becoming the last man to set foot on the lunar surface.
He wrote the initials of his only child in the dust before climbing back into the module.
“I knew that I had changed in the past three days and that I no longer belonged solely to the Earth,” Mr Cernan wrote in a memoir titled The Last Man on the Moon.
“Forever more, I would belong to the universe.”
During the mission’s three days on the Moon, Mr Cernan and Mr Schmitt travelled more than 19 miles (30 km) in a lunar rover vehicle.
They gathered more than 220 pounds (100kg) of rocks during their 22 hours of exploring craters and hills.
NASA administrator Charles Bolden said: “Gene’s footprints remain on the Moon, and his achievements are imprinted in our hearts and memories.”
Mr Cernan had previously gone into space as the pilot of Apollo 10 and was a pilot on the Gemini IX mission.
The Apollo 10 flight flew to within eight miles of the surface of the Moon, a “dress rehearsal” for Neil Armstrong’s historic Apollo 11 mission two months later.
Mr Cernan was the second American to walk in space on the Gemini IX mission in 1966.
He was a former Navy test pilot who grew up in Chicago.
After he left NASA he helped start the Air One airline, worked as an energy and aerospace consultant, served as chairman of an engineering company and was a space commentator for ABC News.
Mr Cernan died at a Houston hospital surrounded by his family.