"Today's spacewalk has officially begun," said a NASA commentator as the space agency broadcast live images of Japanese astronaut Koichi Wakata leading the operation from inside the space station.
The spacewalk began at 7:01 am (1731 IST), a few minutes earlier than planned. It is expected to last six and a half hours.
Veteran spacewalker Rick Mastracchio is making his seventh career spacewalk, accompanied by rookie Mike Hopkins, who is making his first venture outside the global research lab.
The men's first task is to disconnect the failed ammonia pump, which is about the size of a refrigerator.
On the second spacewalk, set for Monday, the astronauts are to remove the pump so it can be replaced with a spare that was already stowed at the ISS.
A third spacewalk is planned for Christmas Day, when the failed pump will be shuttled away and final installations made on its replacement.
However, there is a chance the astronauts will be able to complete all their work in two spacewalks, NASA has said.
The urgent spacewalks were called for this week due to a faulty valve that caused a partial shutdown in the system that regulates equipment temperature at the space station.
Engineers tried to fix the problem from the ground, but eventually decided they needed to replace the ammonia pump.
The six-man crew was never in danger, but NASA wanted to repair the problem sooner rather than later, agency officials said.
NASA also had to rig up some last-minute contingency gear inside the US-made spacesuits, which have not been used since a helmet water leak nearly drowned a European astronaut in July.
