inspect and possibly repair the ammonia leak that affected the US segment of the orbiting laboratory on Thursday.
"Spacewalk under way to repair ammonia leak," said the headline of a US space agency statement. Ammonia is used to cool the station's power system.
However the astronauts did not detect any signs of ammonia leaking into space in the first hour of their mission, Nasatelevision said, adding that they "have reported nothing out of the ordinary so far."
Officials said the emergency spacewalk will set a precedent because it was being conducted at such short notice.
It will be the 168th excursion in support of the orbiting laboratory and the fourth for both Marshburn and Cassidy, who have worked together before.
ISS commander Chris Hadfield and Russian cosmonaut Pavel Vinogradov helped Marshburn and Cassidy suit up for the excursion, inspecting their gear and harnesses and making a series of elaborate checks.
"Good Morning, Earth! A complex & vital day on Space Station," Hadfield tweeted before the spacewalk began.
Nasahas stressed that the lives of the multinational crew were not in danger, but both Russian and US space experts called the leak "serious".
Earlier Saturday, the Russian Space Agency released a statement titled "Man Overboard", saying spacewalks always presented a challenge for ISS crews and mission control on the ground.
"After each such sorties guys come back like they've been through a good battle, with bruised hands and grazed shoulders," Vladimir Solovyov, flight director for the Russian segment of the space station, was quoted as saying.
Norm Knight, Nasa chief flight director, said earlier that the spacewalk would be "precedent-setting" at the space station because it had to be performed on short notice, adding that it was "probably one of the fastest ones" that the US space agency has had to assemble.
Both Marshburn and Cassidy have solid spacewalk experience. Marshburn logged 18 hours 59 minutes during a 2009 mission, while Cassidy recorded 18 hours and five minutes, also in 2009.
Nasa said ammonia was leaking from the same general area as in a previous episode in November last year.
A meteorite or a piece of orbital debris is suspected to have hit the cooling radiator and caused the problem, which International Space Station program manager Michael Suffredini described as an "annoyance because of all the work we have to do to work around the problem."
The issue took a turn for the worse on Thursday when it began leaking about five pounds of ammonia per day, compared with a previous level of five pounds per year.
Hadfield earlier described the leak as a "very steady stream of flakes or bits" of ammonia drifting into space.
The flakes were moving "evenly and repeatedly enough that it looks like they were coming from a point source," he said in a recording of the conversation posted by Nasa.
Hadfield, Marshburn and Russian cosmonaut Roman Romanenko are set to return to Earth early on Tuesday after completing their half-year stint aboard the station.
Cassidy is also set to perform two scheduled spacewalks in July, Nasa said.
Saturday's six-and-a-half-hour spacewalk will not interfere with their planned departure from the space station, Nasa said.