Australia were struggling at 67-3 after Stuart Broad struck twice in two balls to remove David Warner and Marnus Labuschagne before England captain Ben Stokes captured the prize wicket of star batsman Steve Smith.
But they had recovered to 311-5 at stumps on the second day of this five-match series, with opening batsman Khawaja 126 not out and wicketkeeper Alex Carey unbeaten on 52 in an unbroken stand of 91.
That still left Australia 82 runs behind England's first-innings 393-8 declared built on Joe Root's 118 not out.
Australia captain Pat Cummins insisted Thursday his recently-crowned World Test champions had no need to emulate England's ultra-aggressive 'Bazball' style batting, saying: "Somewhere our batters might take 200 balls to get a hundred and that's totally fine."
His words were underlined by Khawaja's 199-ball hundred - his 15th in Tests but seventh in 18 matches since he was recalled last year.
Khawaja completed his century with a late-cut four off Stokes with the often understated left-hander throwing his bat in sheer joy.
"I honestly don't know," Khawaja told reporters when asked about his celebration. "It was the culmination of three Ashes tours in England and getting dropped in two of them.
"I don't read the media but when I'm being sprayed (barracked) by the crowd out there, and as I'm going to the nets, that I can't score runs in England, I guess it was a bit more emotional than normal."
Khawaja, who has batted in several different berths, now averages a colossal 68.72 as an opener - the highest by anyone in to have batted in a minimum 20 Test innings in the position.
He added: "Not that I have a point to prove but it's nice to go out and score runs for Australia and show to everyone that the last ten years hasn't been a fluke."
Khawaja's obdurate stay appeared to have ended when Broad bowled him for 112 in the first over with the new ball but replays revealed the veteran seamer had overstepped the crease for a marginal no-ball.
'Gruelling day'
Broad had earlier reduced Australia to 29-2 as he again got the better of Warner, whom he dismissed seven times during the drawn 2019 Ashes in England.
The left-hander had reached nine on an overcast morning favouring England's quicks when he chased a wide ball from Broad and inside-edged into his stumps.
And the roars of the crowd became deafening next ball when Labuschagne, the world's top-ranked Test batsman, fell for a golden duck after edging a Broad outswinger that was brilliantly caught one-handed low down by diving wicketkeeper Jonny Bairstow.
"It has been a hard gruelling day on a pitch that offered very little but being in this position is a really positive place to be I think," Broad told the BBC.
Stokes' bowling fitness had been called into question by a longstanding left knee injury, but the lively all-rounder struck when he rapped Smith on the back foot with a nip-back ball.
Despite a review, Smith - whose twin centuries in the Ashes opener at Edgbaston four years ago powered Australia to a 251-run win - was lbw for 16.
But as the ball got older and conditions for batting eased, Khawaja and Travis Head checked England's progress with a fourth-wicket stand of 81.
Both left-handers went after Moeen Ali, each hitting the recalled off-spinner for sixes on his Birmingham home ground.
But Stokes kept Moeen, in for the injured Jack Leach, going in what was the bowler's first Test in nearly two years since he 'retired' from all red-ball cricket.
His faith was rewarded when Head, fresh from a hundred in Australia's WTC final win over India at The Oval last week, fell for a typically brisk 50 off 63 balls after dragging a drive off Moeen to Zak Crawley at midwicket.
Australia's 148-4 should have become 148-5 when Cameron Green, on a second-ball nought, charged at a sharply-turning Moeen delivery only for Bairstow to miss a clear stumping opportunity. Moeen eventually bowled Green for 38 but only after the all-rounder had put on 72 with Khawaja.
