Timothy "TJ" Creamer, a NASA flight engineer, sent the Twitter message from his @Astro_TJ account.
"Hello Twitterverse! We r now LIVE tweeting from the International Space Station -- the 1st live tweet from Space! :) More soon, send your ?s," Creamer wrote.
NASA said Creamer was the first astronaut to send an "unassisted" Twitter message from space.
Previous "tweets" from space were actually sent by astronauts by email to the ground and support personnel posted them to their Twitter account.
The US space agency said Creamer was able to use Twitter directly because a software upgrade this week gave astronauts aboard the space station personal access to the Internet via what NASA called the "ultimate wireless connection."
The new communications system gives astronauts access to the Web and will provide them with "direct private communications to enhance their quality of life during long-duration missions," NASA said.
Two other astronauts aboard the space station, commander Jeff Williams and Soichi Noguchi of Japan, also have a Twitter account at @NASA_Astronauts.