The most challenging and exciting aspect of space exploration has been manned spaceflight. Soon after the first satellites were launched, both Soviet and American design teams began work on manned space vehicles. The Soviet team was able to make use of a launch vehicle three times as powerful as the ones then available to NASA, so the USSR was able to choose familiar systems known to be reliable. NASA's need to venture into new technological disciplines, on the other hand, later proved crucial to the success of manned lunar flight — a challenge that the Soviet design teams were unable to meet.

After several unmanned test flights in 1960 and early 1961 the USSR launched the world's first manned spacecraft, Vostok, on Apr. 12, 1961. The pilot was a 26-year-old Russian named Yuri Gagarin. The basic spacecraft consisted of a three-ton sphere and a two-ton service module. The sphere was later rebuilt to hold three crew members and was launched with the name Voskhod in 1964.

In 1961, President John F. Kennedy had declared that the goal of the U.S. manned space program was to land a man on the Moon before the end of the decade. The story of that endeavor is recounted in the entries on the Mercury program, Gemini program, and Apollo program. The landing did take place on schedule, on July 20, 1969. Since those first years of flight the Soviet and U.S. manned programs have taken divergent paths.