Apollo 16 (April 16–27, 1972) was the tenth crewed mission in the United States Apollo space program, administered by NASA, and the fifth and penultimate to land on the Moon. It was the second of Apollo's "J missions", with an extended stay on the lunar surface, a focus on science, and the use of the Lunar Roving Vehicle (LRV). The landing and exploration were in the Descartes Highlands, a site chosen because some scientists expected it to be an area formed by volcanic action, though this proved not to be the case.

The mission was crewed by Commander John Young, Lunar Module Pilot Charles Duke and Command Module Pilot Ken Mattingly. Launched from the Kennedy Space Center in Florida on April 16, 1972, Apollo 16 experienced a number of minor glitches en route to the Moon. These culminated with a problem with the spacecraft's main engine that resulted in a six-hour delay in the Moon landing as NASA managers contemplated having the astronauts abort the mission and return to Earth, before deciding the problem could be overcome. Although they permitted the lunar landing, NASA had the astronauts return from the mission one day earlier than planned.

After flying the Lunar Module to the Moon's surface on April 21, Young and Duke spent 71 hours—just under three days—on the lunar surface, during which they conducted three extravehicular activities or moonwalks, totaling 20 hours and 14 minutes. The pair drove the lunar rover, the second used on the Moon, for 26.7 kilometers (16.6 mi). On the surface, Young and Duke collected 95.8 kilograms (211 lb) of lunar samples for return to Earth, including Big Muley, the largest Moon rock collected during the Apollo missions. During this time Mattingly orbited the Moon in the command and service module (CSM), taking photos and operating scientific instruments. Mattingly, in the command module, spent 126 hours and 64 revolutions in lunar orbit. After Young and Duke rejoined Mattingly in lunar orbit, the crew released a subsatellite from the service module (SM). During the return trip to Earth, Mattingly performed a one-hour spacewalk to retrieve several film cassettes from the exterior of the service module. Apollo 16 returned safely to Earth on April 27, 1972.

John Young, the mission commander, was 41 years old and a captain in the Navy at the time of Apollo 16. Becoming an astronaut in 1962 as part of the second group to be selected by NASA, he flew in Gemini 3 with Gus Grissom in 1965, becoming the first American not of the Mercury Seven to fly in space. He thereafter flew in Gemini 10 (1966) with Michael Collins and as command module pilot of Apollo 10 (1969). With Apollo 16, he became the second American, after Jim Lovell, to fly in space four times.

Thomas Kenneth "Ken" Mattingly, the command module pilot, was 36 years old and a lieutenant commander in the Navy at the time of Apollo 16. Mattingly had been selected in NASA's fifth group of astronauts in 1966. He was a member of the support crew for Apollo 8 and Apollo 9. Mattingly then undertook parallel training with Apollo 11's backup CMP, William Anders, who had announced his resignation from NASA effective at the end of July 1969 and would thus be unavailable if the first lunar landing mission was postponed. Had Anders left NASA before Apollo 11 flew, Mattingly would have taken his place on the backup crew.

Mattingly had originally been assigned to the prime crew of Apollo 13, but was exposed to rubella through Charles Duke, at that time with Young on Apollo 13's backup crew; Duke had caught it from one of his children. Mattingly never contracted the illness, but three days before launch was removed from the crew and replaced by his backup, Jack Swigert. Duke, also a Group 5 astronaut and a space rookie, had served on the support crew of Apollo 10 and was a capsule communicator (CAPCOM) for Apollo 11. A lieutenant colonel in the Air Force, Duke was 36 years old at the time of Apollo 16, which made him the youngest of the twelve astronauts who walked on the Moon during Apollo as of the time of the mission. All three men were announced as the prime crew of Apollo 16 on March 3, 1971.

Apollo 16's backup crew consisted of Fred W. Haise Jr. (commander, who had flown on Apollo 13), Stuart A. Roosa (CMP, who had flown on Apollo 14) and Edgar D. Mitchell (LMP, also Apollo 14). Although not officially announced, Director of Flight Crew Operations Deke Slayton, the astronauts' supervisor, had originally planned to have a backup crew of Haise as commander, William R. Pogue (CMP) and Gerald P. Carr (LMP), who were targeted to become the prime crew on Apollo 19. However, after the cancellations of Apollos 18 and 19 were announced in September 1970, it made more sense to use astronauts who had already flown lunar missions as backups, rather than training others on what would likely be a dead-end assignment. Subsequently, Roosa and Mitchell were assigned to the backup crew, while Pogue and Carr were reassigned to the Skylab program where they flew on Skylab 4.

For projects Mercury and Gemini, a prime and a backup crew had been designated, but for Apollo, a third group of astronauts, known as the support crew, was also designated. Slayton created the support crews early in the Apollo Program on the advice of Apollo crew commander James McDivitt, who would lead Apollo 9. McDivitt believed that, with preparation going on in facilities across the U.S., meetings that needed a member of the flight crew would be missed. Support crew members were to assist as directed by the mission commander. Usually low in seniority, they assembled the mission's rules, flight plan, and checklists, and kept them updated. For Apollo 16, they were: Anthony W. England, Karl G. Henize, Henry W. Hartsfield Jr., Robert F. Overmyer and Donald H. Peterson.