Australia's remarkable Ashes fightback left England staring at a first innings total of 527 for seven on Friday and the loss of two late wickets on day two of the third test made the task look even more imposing.
England were 52 for two at stumps after painstaking play.
With his under-pressure side 2-0 down in the five-match series, Australia captain Michael Clarke earlier led from the front and moved on from his overnight 125 to craft a near chanceless 187 - his highest test score against England.
His bold declaration after tea caught many at Old Trafford on the hop but his statement of intent was heeded by his bowlers, who kept things tight against nervous England batsmen.
England captain Alastair Cook was unbeaten on 36 and Jonathan Trott on two after Lord's centurion Joe Root edged in-form quick Peter Siddle behind for eight from 57 deliveries and nightwatchman Tim Bresnan (1) seemed to do the same.
However replays suggested no nick, but he did not review.
"Bresnan heard a noise so he obviously thought he hit it," England off-spinner Graeme Swann, who took five for 159, told a news conference.
"Australia are in a good position, I don't know if they are in an ideal position to win a test match as we have only lost two wickets in our first innings. The fact Cook is still there is good for us as he is due a big score."
Cook, who has a slight back problem, survived on 15 when he edged returning off-spinner Nathan Lyon on to wicketkeeper Brad Haddin's knee and the ball dropped just short of a flat-footed Clarke at slip.
But Clarke's day was to be remembered for his batting as he further inspired his side before finally falling when tiredness got to him. He was bowled, awkwardly playing on to Stuart Broad.
Australia had not bagged a century in the series but Clarke, who hit Bresnan for three straight fours as he passed 150, began to turn the tables on those who laughed at his prediction of a 3-2 series win after the second test humbling at Lord's.
His wicket was Broad's 200th in test cricket but it was scant consolation for England, who have laboured under the Old Trafford sun and saw Steve Smith (89), Chris Rogers (84), Haddin (65 not out) and Mitchell Starc (66 not out) rack up handy scores on a largely flat pitch.
Swann removed Smith when the number five gave away his wicket by skying a top-edged sweep to Jonny Bairstow in the off-spinner's first over of the day.
His dismissal prompted the return of David Warner.
The left-hander punched England's Joe Root in a Birmingham bar during June's Champions Trophy, leading to a ban from the Australia side, but he was drafted back in for this test with the batsmen previously struggling.
Warner was widely booed and taunted from the packed stands as he walked to the crease.
He was initially watchful but got a thick edge on five off Swann, the ball hitting wicketkeeper Matt Prior's knee and bouncing up for slip Jonathan Trott to take the catch.
Warner conferred with Clarke and reviewed, but replays showed a clear nick and there was nothing wrong with the catch.
Warner's review came after controversy on Thursday when Usman Khawaja was given out by the on-field and third umpires despite not appearing to edge Swann behind. Cricket Australia asked the ICC for clarification over the "incorrect" call.
The jubilant crowd waved Warner back to the dressing room with glee, leaving Haddin to come in and steady Australia.
He had a bit of luck when his inside edge was dropped on 10 by Prior off the unusually misfiring James Anderson, who ended with nought for 116 on his Lancashire home ground.
Clarke, who won the toss, then got out and left the field to wild applause from the posse of green and gold clad Australians in the vast temporary stand at the revamped Manchester venue.
Siddle (one) was Swann's fifth victim when bowled as spin looked to be the way forward for the rest of the test, with Lyon impressing and pacemen struggling to extract reverse swing.
Early rain hit famously wet Manchester but the sun came out just before the start. Showers are possible on Saturday though, with the damp bowlers' footholes already causing problems.