They'll be aboard the station for four and a half months.
Fischer and Yurchikhin reached the $US100 billion space station, which orbits about 400 km above Earth, arrived on schedule at 10:18pm (AEST).
"I know I speak for Fyodor when I say if we could figure out how to fit [our wives] Larisa and Elizabeth in that seat, that is who we would take with us", said Fischer in jest at a media briefing on April 19, clarifying that their third seat will carry cargo for the ISS.
Expedition 51 crewmembers Fyodor Yurchikhin of Roscosmos (left) and Jack Fischer of NASA (right) answer questions from the press at the Gagarin Cosmonaut Training Facility in Star City, Russia. Russian Federation last launched a crew of two in 2003, when Expedition 7 Commander Yuri Malenchenko and Flight Engineer Ed Lu launched to the space station from Kazakhstan.
Nespoli will then join the two this coming July, when he flies to the ISS on a three-person Soyuz MS-05 spacecraft.
Another Russian-American duo, Yuri Malenchenko and Edward Lu, undertook the last two-man mission to the ISS, in April 2003.
"We are looking forward to intensifying our cooperation on a positive agenda, what the European Union and China can do together for the benefit not only of our citizens, but also of the world", Mogherini said.
The crew comprises Russian cosmonaut Fyodor Yurchikhin and NASA astronaut Jack Fischer.
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Fischer and Yurchikhin are scheduled to remain aboard the Station until September, along with Whitson, whose stay aboard the Station was extended into Expedition 52 by an agreement recently signed between NASA and Roscosmos.
Fischer, a first-time space flier, and Yurchikhin, a veteran of four spaceflights, will spend more than 4 months aboard the orbiting laboratory before returning to Earth in early September.
Thus the overall station crew complement of astronauts and cosmonauts increases to five - from the US, Russia and France - representing their respective space agencies and countries.
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It's rare for the United States or Russian Federation to launch a crew of just two astronauts.
Fischer and Yurchikhin were the first to receive permission from Roscosmos to name their Soyuz - "Argo".
Yurchikhin marks his fifth space launch with this event.More news: Russian Federation vetoes United Nations resolution on Syria gas attack probe