Apollo 16 was the first mission to land humans in the Moon’s Descartes Highlands.
Apollo 16 landed on April 21, 1972, carrying commander John Young and lunar module pilot Charles Duke to the Descartes region. The mission was designed to investigate the lunar highlands, an ancient, bright terrain that had not previously been visited directly by astronauts. Young and Duke spent more than 20 hours conducting surface activities and used the Lunar Roving Vehicle to travel beyond the immediate landing area.
Scientists had expected the Cayley and Descartes formations to contain volcanic rocks. Samples collected by the astronauts instead showed that much of the terrain consisted of breccias and other materials shaped by enormous impacts. The mission helped overturn the idea that the region’s appearance proved widespread lunar volcanism.
Apollo 14 and Apollo 15 had sampled highland-derived material, but neither had landed in the highlands themselves. Apollo 17 later landed in the Taurus–Littrow valley, not Descartes. That distinction makes Apollo 16 the single canonical answer to this question.