Stephen Bowen and Alvin Drew have a long list of repairs to make. They will also be conducting an experiment to capture the invisible vacuum of space.
This was the first of two spacewalks planned for discovery's farewell flight.
Bowen and Drew will go back out Wednesday for one last spacewalk.
The space shuttle Discovery docked at the space station Saturday, but it took longer than usual to get the hatches between the two open.
That delayed the astronauts' first mission to attach an equipment platform. It was finally installed late Saturday night.
After this flight, Discovery will be retired and sent to the Smithsonian Institution.
The Associated Press contributed to this report.