Christina Koch and Andrew Morgan had to remove a pair of old batteries and install a new one delivered just a week ago.
These new lithium-ion batteries are so powerful that only one is needed for every two old ones, which are original to the orbiting lab.
The 180kg (400lb) batteries — half the size of a refrigerator — are part of the space station’s solar power network.
Astronauts have been upgrading them since 2017 and are halfway there.
These latest battery swaps are especially difficult given the extreme location on the station’s sprawling frame.
It is too far for the 58ft (17 metre) robot arm to reach, forcing Koch and Morgan to lug the batteries back and forth themselves.
That is why so many spacewalks are needed this time to replace the 12 old nickel-hydrogen batteries with the six new lithium-ion versions.
Morgan savoured a South American sunrise as the spacewalk got under way.
“Oh my goodness,” he said. “Pretty awesome.”
Half-an-hour later, as the station soared 250 miles (400km) above the Mediterranean, Koch asked: “What are we flying over? It’s beautiful.”
Nasa plans to wrap up the five battery spacewalks this month, followed by a Russian spacewalk.
Then five more US-Italian spacewalks will be conducted in November and December to fix a key science instrument.
Nasa is calling it a “spacewalk bonanza”.
This unusual run of spacewalks will feature the first all-female spacewalk — by Koch and Jessica Meir — later this month.
Koch is two-thirds of the way through a more than 300-day mission. It will be the longest single spaceflight by a woman.