The first human spaceflight was undertaken on April 12, 1961, when cosmonaut Yuri Gagarin made one orbit around the Earth aboard the Vostok 1 spacecraft launched by the Soviet Union.

Valentina Tereshkova became the first woman in space on board Vostok 6 on June 16, 1963. Both spacecraft were launched by Vostok 3KA launch vehicles. Alexei Leonov made the first spacewalk when he left the Voskhod 2 on March 8, 1965. Svetlana Savitskaya became the first woman to do so on July 25, 1984.

The United States became the second nation (and for four decades, one of only two) to achieve manned spaceflight, with the suborbital flight of astronaut Alan Shepard aboard Freedom 7, carried out as part of Project Mercury. The spacecraft was launched on May 5, 1961 on a Redstone rocket.

The first U.S. orbital flight was that of John Glenn aboard Friendship 7, which was launched February 20, 1962 on an Atlas rocket. Since April 12, 1981 the U.S. has conducted all its human spaceflight missions with reusable Space Shuttles. Sally Ride became the first American woman in space in 1983. Eileen Collins was the first female Shuttle pilot, and with Shuttle mission STS-93 in July 1999 she became the first woman to command a U.S. spacecraft.

The People's Republic of China became the third nation to acheive human spaceflight when astronaut Yang Liwei launched into space on a Chinese-made vehicle, the Shenzhou 5, on October 15, 2003. This flight made China the third nation capable of launching its own manned spacecraft using its own launcher. Previous European (Hermes) and Japanese (HOPE-X) domestic manned programs were abandoned after years of development, as was the first Chinese attempt, the Shuguang spacecraft.

The furthest destination for a human spaceflight mission has been the Moon, and as of 2007 the only missions to the Moon have been those conducted by NASA as part of the Apollo program. The first such mission, Apollo 8, orbited the Moon but did not land.

The first Moon landing mission was Apollo 11, during which, on July 20, 1969, Neil Armstrong became the first person to set foot on the Moon. Six missions landed in total, numbered Apollo 11–17, excluding Apollo 13. Altogether twelve men reached the Moon's surface, the only humans to have been on an extraterrestrial body. The Soviet Union discontinued its program for lunar orbiting and landing of human spaceflight missions on June 24, 1974 when Valentin Glushko became General Designer of NPO Energiya.

The longest single human spaceflight is that of Valeriy Polyakov, who left earth on January 8, 1994, and didn't return until March 22, 1995 (a total of 437 days 17 hr. 58 min. 16 sec. aboard). Sergei Krikalyov has spent the most time of anyone in space, 803 days, 9 hours, and 39 seconds altogether.

The longest perdiod of continuous human presence in space lasted as long as 3,644 days, eight days short of 10 years, spanning the launch of Soyuz TM-8 on September 5, 1989 to the landing of Soyuz TM-29 on August 28, 1999.

For many years beginning in 1961, only two countries, the USSR (later Russia) and United States, had their own astronauts. Later, cosmonauts and astronauts from other nations flew in space, beginning with the flight of Vladimir Remek, a Czech, on a Soviet spacecraft on March 2, 1978. As of 2007, citizens from 33 nations (including space tourists) have flown in space aboard Soviet, American, Russian, and Chinese spacecraft.