The tourists have four wickets left and will go into Monday's fifth day without their front-line batsmen after a confrontational and tense day's cricket. Rain is forecast on the final day.
At the close, England were fighting hard at 247 for six with Matt Prior on 31 and Stuart Broad not out 22. They trailed Australia by 284 runs.
"We know it's not going to be easy, the boys at the lower end have troubled us in the past so we've got to come prepared, be switched on and give it to them early in the morning," Australia paceman Peter Siddle said.
England had a minor triumph when they passed 200 for the first time in four innings in the series, but defeat looked inevitable after losing the first Gabba Test by 381 runs.
Joe Root, elevated to the number three spot vacated by Jonathan Trott, showed plenty of fight to hold out for 267 minutes for 87 while Kevin Pietersen contributed 53 off 99 balls.
"If there's a bit of weather about I think we might be able to (save it)," Root said. "I think we're obviously up against it. I thought Mattie (Prior) and Stuart (Broad) were exceptional and they're going to have to continue to do that again tomorrow as well."
Debutant Ben Stokes dug in and resisted for 90 balls before he was caught at second slip off Ryan Harris for 28 with six overs left in the day. Stokes had an ugly brush of shoulders with Mitchell Johnson in the previous over.
Root (87) missed out on his third Test century in unfortunate circumstances. He played back to spinner Nathan Lyon and got an inside edge that ran off his pad for wicketkeeper Brad Haddin to dive forward and take his 200th Test catch.
Siddle grabbed the crucial breakthrough, ending England's first century partnership of the series when he bowled Pietersen off an inside edge.
And shortly before tea, Ian Bell was out for six after playing an injudicious shot off leg-spinner Steve Smith.
Pietersen put on 111 runs for the third wicket with Root after the tourists lost openers Alastair Cook and Michael Carberry cheaply.
It was a big wicket for Australia, with Pietersen having scored 227 and 158 in his previous two Ashes Tests at the ground. It was the ninth time Siddle has dismissed Pietersen in Tests, including twice in this match.
Senior batsman Bell hung his head after belting a Smith full-toss to man of the moment Mitchell Johnson, who took a sprawling catch at mid-on. Bell had top-scored with an unbeaten 72 in England's first innings of 172.
Michael Clarke declared Australia's second innings at the overnight score of 132-3, and England, who beat Australia 3-0 at home earlier this year, got off to a shaky start, losing Cook for one in Johnson's opening over and Carberry 10 overs later. Cook's scalp was Johnson's eighth wicket of the match after he captured seven for 40 in England's first innings. The left-arm paceman now has 17 wickets in the series.
The skipper was out to Johnson's third ball of his opening over, hitting the ball straight to Ryan Harris at fine leg.
It was a demoralising moment for England, needing to occupy the crease and bat out the final two days. The cheap dismissal completed a dire Test for Cook, who was spectacularly bowled by Johnson for three in the first innings.
In his past seven tests against Australia, the England captain has scored 359 runs at an average of 25.
Carberry, who made 60 in the first innings, was out hooking Siddle for 14 in the 12th over, leaving England 20-2. Lyon, positioned on the fine leg rope, took the catch just above the ground.
-- Australia 1st innings 570 for 9 declared (M. Clarke 148, B. Haddin 118; S. Broad 3-98)
-- England 1st innings 172 (I. Bell 72 not out, M. Carberry 60; M. Johnson 7-40)
Fall of wickets: 1-4 (Rogers), 2-4 (Watson), 3-65 (Clarke)
Bowling: Anderson 7-1-19-2, Broad 6-0-19-0, Swann 9-3-31-0, Stokes 7-3-20-0, Panesar 10-0-41-1