In a contest reduced to 39 overs per side, Harry Brook followed up his maiden ODI hundred on Tuesday with a scintillating 87 off 58 balls before Liam Livingstone's staggering demonstration of six-hitting.
Livingstone belted seven in total, including four in Mitchell Starc's final over which yielded 28, to equal Andrew Flintoff's record for the most sixes in an ODI at Lord's as England posted 312 for five.
Australia raced to 68 without loss in reply but stumbled to 96 for six after Brydon Carse and Jofra Archer, in his first ODI at the home of cricket since the 2019 World Cup final, turned up the heat.
On a sticky pitch offering assistance under lights, the pair each exceeded 90mph to take five of the first six wickets. Carse finished with three for 36 with Archer collecting two for 33.
Matthew Potts claimed four for 38 as England backed up their win in Chester-le-Street this week and the momentum is now firmly with them, having come from 2-0 down to level the five-match series at 2-2.
Another triumph over the 50-over world champions was built on a fantastic batting display after rain delayed the start by more than two hours although Australia were initially on top having won the toss.
Starc and Josh Hazlewood were exemplary, settling into Test-match lengths in helpful conditions to repeatedly trouble England's openers. While Ben Duckett showed his experience by battling through, Phil Salt sliced Hazlewood to Marnus Labuschagne while Will Jacks did likewise off Mitchell Marsh.
Brook looked to be on his way for 17, strangled down leg, but replays showed the ball had grazed the turf before reaching Josh Inglis. Jeers rained down but this was more of a storm-in-a-teacup than what unfolded after Alex Carey's controversial stumping of Jonny Bairstow in last year's Ashes.
Duckett (63 off 62 balls) thrashed the first of England's dozen sixes - a Lord's record in an ODI - when he advanced to Adam Zampa but the leg-spinner had his revenge when a top-edged sweep sailed to Sean Abbott.
Brook, though, looked in irresistible touch, piercing the gaps for back-to-back fours off both Zampa and Glenn Maxwell. Zampa's mixed fortunes continued when he overpitched to Jamie Smith and went the distance before a drag down to Brook three balls later was also clattered over the leg-side boundary.
Even Hazlewood's brief return did little to discourage Brook, who scooped then swivel pulled the seamer for fours. Another century seemed to be there for the taking but he could not get enough elevation to clear long-on off Zampa, who conceded 66 in eight overs on his comeback from illness.
After Smith lost his shape attempting to tee off at Maxwell and miscued to Hazlewood to depart for 39, Livingstone finished England's innings in a blaze of sixes.
The last over was particularly brutal as England threatened to fall short of 300, with Starc laced for 28 as Livingstone swung with carefree abandon, taking four sixes and a four en route to a 25-ball fifty, the fastest in an ODI at Lord's.
With Australia set the equivalent of 400 in a regulation ODI, Marsh and the returning Travis Head tried to lay down an early marker. Matthew Potts struggled with his line and bowled a nine-ball over, although Archer repeatedly beat the edge of Head and was unlucky a top edge off Marsh hit the turf.
Head seemed to have found his range when he hammered Carse over the Mound Stand but Australia's innings was sent into an irreversible tailspin when he was castled in the fast bowler's next over.
Steve Smith inside edged Potts through to Jamie Smith before a fired-up Archer beat Marsh all ends up, with the Australia captain groping forwards only to have his off stump emphatically knocked back.
Labuschagne was greeted with a vicious short ball that rapped him on the forearm before being bowled by a borderline unplayable delivery that pitched on middle and knocked off stump out the ground from Archer, who earlier in the over accounted for Josh Inglis.
When Maxwell under-edged Archer to Smith, Australia had lost six wickets in 43 legitimate deliveries as their hopes of moving into an unassailable lead in the series evaporated.
Potts claimed a further three wickets as Australia were all out for a sorry 126 in 24.4 overs.