Apollo I - Although Apollo I never officially lifted off from Kennedy Space Center, it became America's first space tragedy when three astronauts were killed in a fire which swept through the command module during a routine systems test.
Virgil "Gus" Grissom
Soyuz I - The first launch of the Soyuz spacecraft (still in use today) was supposed to rendezvous with a second Soyuz spacecraft, but that launch was scrubbed after Komarov reported problems with deploying the craft's solar panels. After a day in orbit, Soyuz I was ordered back to land. During reentry, the main chute did not deploy. Komarov deployed the reserve, but became entangled with the main, and the Soyuz I descent module crashed into the ground. Komarov became the first official spacefaring fatality.
Soyuz XI - This mission was the first to link up to Salyut I, the first space station. The mission itself was supposed to last 30 days, but the mission was cut short due to a small fire in the station and difficult working conditions. Upon separation from the Salyut, a pressure valve was accidently loosened. One of the cosmonauts attempted to reseal it, but all the oxygen leaked out of the capsule. Although the capsule automatically deployed its chute and made a soft landing, the crew of three were found dead in their seats.
STS 51L - The United States' first in-flight space stragedy. 73 seconds into the flight, the space shuttle Challenger exploded in a fireball, killing all seven astronauts aboard. The crew included Christa McAuliffe, a civilian who was to have become the first teacher in space. An investigatory panel later determined the cause of the explosion to be a faulty O-ring on one of the solid rocket boosters (SRB).