Australia, seeking to complete a clean-sweep of the white-ball component of the Ashes series, posted 5-162 at Adelaide Oval on Saturday night.
Mooney was superb, striking 10 fours in her 63-ball knock - her 25th half-century in T20 internationals.
Australia lead the three-match T20 series 2-0, having swept the preceding 50-over series 3-0.
The host nation won the toss and were given a solid platform by opening batters Mooney and Georgia Voll - the pair posted a half-century partnership from 41 balls.
Just six balls later, the stand ended on 56 when Voll (23 from 21 deliveries) was caught at deep wide mid-on from the spin bowling of Alice Capsey (1-25).
But Mooney continued on her merry way, the veteran scoring with a vast array of strokes, including an audacious ramp shot from pace bowler Lauren Filer that went for four.
At the midpoint of the innings, Australia were 1-76 and England struck again in the 12th over when Phoebe Litchfield (12 from 10 balls) missed an attempted sweep from left-arm tweaker Sophie Ecclestone (1-37).
Mooney reached her half-century from 41 balls and then accelerated as Ellyse Perry (12 from 11 balls), Grace Harris (11 from 10) and Annabel Sutherland (three from three) fell cheaply.
After the series-ending T20 in Adelaide, the rivals will play a one-off Test match at the MCG starting on Thursday.Â
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