Jofra Archer took six wickets to help England bundle out Australia for 225 and gain a crucial first-innings lead despite another masterful knock from Steve Smith.
The star batsman boasts 751 runs in just six innings, 377 runs more than the next highest run-getter in the series.
Smith seemed well-set for a three-figure score but fell to an inswinging Chris Woakes delivery trapping him plumb in front of the wicket for a healthy contribution of 80.
Although Australia's proverbial tail wagged for a while, they still face a first-innings deficit of 69 with paceman Archer claiming spectacular figures of 6-62.
Smith came into bat in familiar circumstances as Australia crumbled to 14-2 in reply to England's total of 294.
He was cautious in the start of his innings, uncharacteristically failing to connect cover drives off deliveries pitched wide of the off-stump.
Nevertheless, the former Australia skipper soon found his touch and brought his 10th consecutive fifty-plus score against traditional rivals England by an expansive hoick over midwicket for a maximum.
Smith quickly ran out of partners on the other end as he withstood England's pace attack alone for the majority of Australia's innings.
He had a lucky escape in the post-tea session when a chance offered from his bat was shelled by home side captain Joe Root in the slips.
But the drop did not hurt England too much as Smith could not negotiate a delivery from Woakes seaming into his pads.
David Warner, also returning from a 12-month ban due to ball-tampering like Smith, failed for the umpteenth time in the series.
He was dismissed in single figures for the eighth time in nine innings, managing to accumulate a paltry sum of 84 runs across the five games.
The 32-year-old was adjudged not out on the field before Root chose to review the decision and the replays indicated a clear spike on Ultra Edge as the ball went past the bat.
Archer then had Marcus Harris edge one to Ben Stokes, who held onto a sharp chance at second slip.
Smith and Marnus Labuschagne, his concussion replacement in the Lord's Test, later tried to ameliorate the state of Australia's innings.
The 69-run stand between the two was once again broken by Archer, who trapped Labuschagne lbw two short of his half-century.
Wickets came in a jiffy after tea when Archer removed Mitchell Marsh while the returning Sam Curran struck on successive balls to send Tim Paine and Pat Cummins back to the pavilion.
Smith's dismissal left Australia reeling at 187-8 staring at a deficit in excess of 100 but Peter Siddle and Nathan Lyon played enterprising strokes to reduce England's lead.
Archer eventually cleaned up the tail thanks to an incredible grab from Rory Burns to get Siddle out.
Earlier, England were unsuccessful in breaching the 300-run mark and could add just 23 runs to their overnight score.
Jos Buttler top-scored for the hosts with a counter-attacking 70 as Australia's Marsh completed his maiden five-wicket haul on his return to the Test side.