Russian cosmonaut Oleg Kononenko, American astronaut Anne McClain, and Canadian astronaut David Saint-Jacques successfully launched at 6:31 a.m. ET from the Baikonur Cosmodrome in Kazakhstan and went into orbit a short time later.
NASA said, the launch comes less than two months after a booster failure forced a Soyuz spacecraft carrying Russian cosmonaut Alexey Ovchinin and United States astronaut Nick Hague to make an emergency landing.
Kononenko, McClain and Saint-Jacques smiled and gave thumbs up to the cheering crowd including relatives as they ascended into the Soyuz capsule.
At a press conference on the eve of the launch, crew commander Kononenko said the astronauts "absolutely" trusted teams preparing for the flight.
Aboard the International Space Station, he will conduct a number of science experiments, with some focusing on the physical effects of the weak gravity astronauts experience in orbit as well as how to provide remote medical care.
"We are psychologically and technically prepared for blast-off and any situation which, God forbid, may occur on board", the 54-year-old said. It is the first mission since an aborted launch in October. "We feel very ready for it", she said. A Russian investigation attributed the failure to a sensor that was damaged during the rocket's final assembly.
A Russian Soyuz rocket rises from the Baikonur Cosmodrome in Kazakhstan, carrying three spacefliers into orbit.
In a successful rehearsal for today's flight, a Soyuz cargo vessel took off on 16 November from Baikonur and delivered several tonnes of food, fuel and supplies to the ISS.
Now that crewed flights have resumed, Gerst and two other crew members, NASA's Serena Auñón-Chancellor and Russia's Sergey Prokopyev, are due to head back to Earth on December 19.
During their mission, members of the crew are scheduled to embark on a spacewalk to further probe a mysterious hole that caused a loss of air pressure on-board the ISS in August.
After NASA retired the Space Shuttle in 2011, Russian Soyuz rockets have been the only way to get people to the International Space Station.