Stuart Broad was left one wicket short of a famous milestone - on 399 in Tests - while Steve Smith bagged yet another in his prolific series as he joined Garfield Sobers as the second-quickest batsman to 6,000 runs.
Half-centuries from Khawaja (91no) and David Warner (56) were the most telling contributions, however, as the hosts reached 193-2 at stumps in reply to 346 all out.
England’s tailenders responded well to the early loss of Dawid Malan (62) to add 113 for their last five wickets, despite Pat Cummins’ 4-80 on his home ground.
Then, however, the fine margins did not favour Joe Root’s men as several edges went to ground or just wide of the fielders after Broad had given them an early boost when he bowled opener Cameron Bancroft for a duck to move to 399 wickets.
The morning session was full of flawed but often entertaining cricket, interspersed with occasional brilliance.
Very much in the last category was Smith’s memorable catch at second slip, diving low to his left to hold on one-handed off Mitchell Starc and end Malan’s four-hour, 180-ball vigil.
England’s last specialist batsman added only seven to his overnight score, and those who had cited a fragile tail before this match began were predicting a hasty flake-out from 251-6.
It did not turn out that way, thanks to spirited batting - and some awful out-cricket from Australia.
Cummins uncharacteristically put down a straightforward chance from a poor shot by Tom Curran off Nathan Lyon at mid-on.
Then immediately given the chance to put right his error when Smith introduced him into the attack at the other end, Cummins had to watch in disbelief as Josh Hazlewood failed to even touch an easier catch at midwicket after a hapless flap at a short one by Moeen Ali.
It was a passage of play which would not have been out of place a couple of miles up the road on Bondi Beach.
But credit nonetheless to England, who took advantage with stands of 43 and then 41 for the seventh and eighth wickets as Broad - emboldened perhaps by his 50 in Melbourne last week - rode his luck with some big-hitting on the hook.
Moeen had by then gloved a good short ball behind off Cummins, and Curran propped another to short-leg, before Broad contrived to mistime a slog at Nathan Lyon so badly that it skewed gently back over his own head for an unmissable slip catch.
There was still an appropriately comedic end of the innings to come, when Mason Crane was last out in a run-out mix-up with James Anderson over an attempted leg-bye single.
Broad then wasted no time beating Bancroft’s loose defence with just his second delivery to bowl the opener through the gate.
Warner predictably proved a tougher nut to crack, but Anderson had the answer with an off-cutter which took the outside-edge for caught-behind to break a stand of 85 just before tea.
England were disciplined with the ball, but Khawaja brought up his 50 by using his feet for a straight six off Moeen, and Smith reached his 6,000 in his 111th innings - 43 more than Don Bradman but the same as Sobers - in an unbroken century partnership.