A late collapse saw Charlotte Edwards' side bowled out short of Australia's 203 for eight.
Edwards' 61 at the top of the order was the lone hand as England lost seven for 34 following the skipper's departure.
Defeat means England fell 4-2 points behind in an innovative series decided by results in Test, 50-over and Twenty20 matches.
After last week's only Test at Wormsley ended in a draw - meaning two points were shared - Australia snuck ahead in the series today thanks to their slow bowlers.
Spin duo Jess Jonassen (four for 38) and Erin Osborne (three for 39) did the majority of the damage to an England order that did not help themselves with a pair of run outs as they were bowled out for 176 in 47.3 overs.
Katherine Brunt had earlier taken three for 29 to restrict Australia after opener Meg Lanning hit 56 from 64 balls.
The series continues at Hove on Friday for the second of three ODIs. Three more Twenty20s will follow, meaning there are 10 points still up for grabs.