A fine knock of 81 by Australian No.3 Jess Cameron couldn't stop the hosts bouncing back from defeat in the opening ODI with a 51-run win at Hove on Friday.
The points-based, multi-format series is now level at four-points all with four games to play - another 50-over game on Sunday followed by three Twenty20 clashes.
Set a tough target of 257 after England won the toss and chose to bat, Australia were always on the back foot with openers Rachael Haynes and Meg Lanning both dismissed for ducks.
Reliable first-drop batter Cameron offered some hope but she received little support with spin bowler Jess Jonassen (34 not out) the second-highest scorer as Australia were bowled out for 205 in 48.2 overs.
"It (the loss) is a bit hard to take in at the moment," said Cameron, who passed 1000 career ODI runs during her knock.
"There's a lot things we need to work on but there's a lot of positives we can take out of today and there's a few more games to go yet.
"We're looking forward to getting out here on Sunday and proving why we're ranked number one in all formats."
England had five different wicket takers with Katherine Brunt and Holly Colvin claiming two each.
The hosts made 6-256 from their 50 overs with a strong team effort.
Captain and opener Charlotte Edwards' top-scored with 53 and was backed up by handy knocks from Lydia Greenway (46), Arran Brindle (42), Sarah Taylor (32) and Heather Knight (31).
Jonassen (2-29) and Sarah Coyte (2-55) were the pick of Australia's bowlers but the visitors must now regroup ahead of the third one-day match in Hove on Sunday.
The one-day world champions are chasing their first Ashes win on English soil since 2001.
The first match of the series, and only Test, was drawn.