The cigar-shaped Soyuz booster rocket lifted off on Friday morning from the vast Central Asian steppe into the clear dawn sky at 0646 (0046 GMT), leaving only a white puff behind its orange flame.
Since the US shuttle Columbia disintegrated on re-entry over Texas in February 2003, killing all seven astronauts on board, Russia has been sending missions to the station on smaller, single-use Soyuz spacecraft.
The new ISS crew - Russian commander Sergei Krikalev and US astronaut John Phillips - is scheduled to host the Discovery a month from now when it becomes the first US space shuttle to dock at the station since the Columbia tragedy.
About 10 minutes after the launch from the Baikonur cosmodrome, which Russia leases from the former Soviet republic, the crew's capsule separated from the Soyuz rocket and started its solo flight to the ISS.
The successful launch was accompanied by applause from space officials, relatives and friends of the crew.
European Space Agency astronaut Roberto Vittori, 40, blasted off with Krikalev and Phillips and will spend 10 days in orbit conducting scientific experiments. He will return to Earth on 25 April with the outgoing ISS crew, Russian cosmonaut Salizhan Sharipov and American Leroy Chiao, who have been in orbit since October.
The launch was applauded by space
officials and relatives of the crew
Krikalev, 46, is a veteran of three long-duration space flights and two shuttle missions. Phillips turned 54 on Friday.
"This launch was a complete success," Anatoly Perminov, head of Russia's space agency Roskosmos, said. "But we are looking into the future and are working on a multiple-use spacecraft called Clipper," he said.
Perminov said the full-size metal model of the Clipper was being demonstrated in Japan and would also be shown at space and aviation shows in Moscow and Paris this year. But he did not say when the Clipper, designed to take up to six astronauts into space, could make its maiden trip.
"We've tried to minimise the risk as much as possible"
Nasa official Frederick Gregory
The US space shuttle's redesigned fuel tank passed a critical test on Thursday, boosting confidence that a two-year quest to recover from the Columbia accident was nearly over. The launch window for the Discovery opens on 15 May and closes on 3 June.
"Our international partners have worked with us very well, and all of us are very anxious about the (shuttle's) launch," Frederick Gregory, deputy administrator of the US space agency Nasa, said in Baikonur.
"We've tried to minimise the risk as much as possible."
The Discovery will deliver critical equipment to the ISS and test in-flight heat shield repair techniques.