Tim Murtagh's fourth 10-wicket match haul of his career was not enough to ease Middlesex's relegation worries as Durham's batting allowed them to strengthen their grip on the LV= County Championship Division One match at Lord's.
Gordon Muchall, batting at number eight, scored an unbeaten 74 to lead them from 139 for six to 294 all out in their second innings, setting Middlesex a victory target of 396.
Paul Collingwood chipped in with his second half-century of the match, while home captain Chris Rogers was out fifth ball once again.
He was lbw to fellow Australian John Hastings when aiming to midwicket but Sam Robson survived a confident shout from Chris Rushworth to reach 34 not out before Middlesex closed on 44 for one.
Batting was never easy on an overcast day when the ball swung and Murtagh followed his 5-106 in the first innings with 5-86.
Toby Roland-Jones also bowled a good spell in the afternoon, frequently beating the bat. But his only victim was Ben Stokes, lbw for 15, until Rushworth was brilliantly caught at extra cover by Rogers.
WICKET! Hastings strikes early, sending his fellow Australian Rogers back to the pavilion lbw for 4. Middlesex are 6-1, needing 390 to win.
— Durham Cricket Club (@DurhamCricket) September 11, 2014
Having snared Durham's top three in the opening seven overs of the game, Murtagh removed the top four second time around.
He had already bowled Keaton Jennings the previous evening and the others all edged swinging deliveries to wicketkeeper John Simpson.
Makeshift opener Phil Mustard added only four to his overnight 21 before edging a lavish drive, then Mark Stoneman shrugged off his injury scare to go in at number four.
He was shaping to turn Murtagh to leg when he departed for a duck and Scott Borthwick fell to the first ball he faced after lunch after battling all morning to add 23 to his overnight seven.
Michael Richardson rode his luck as eight of his 40 runs came from overthrows, and a further eight from top-edged pulls before Neil Dexter bowled him.
LISTEN: Murtagh claimed a 4th 10-wkt haul in Championship cricket but admits we'd rather be in Durham's position... http://t.co/W6zoF5nD9J
— Middlesex Cricket (@Middlesex_CCC) September 11, 2014
At 99 for five the match was in the balance, but Collingwood took a fancy to the short leg-side boundary and cleared it three times.
Ollie Rayner, given one over before lunch and recalled for two in mid-afternoon, was turning the ball towards that boundary and Collingwood lifted him over the rope to reach 50 off 70 balls.
He inside-edged Steven Finn to give Simpson his fourth catch and depart for 58 in the over before tea, but he had put on 79 with Muchall and the lead was 319.
Muchall enjoyed some good fortune in surviving Roland-Jones' probing spell, but his confidence visibly grew once he began to stroke the ball through the covers.
His ninth four, driven through extra cover off Dexter, took him to 50 off 83 balls - a first half-century since making 158 not out at Trent Bridge in May.
Hastings and Rushworth both put bat to ball to stretch the lead before Rayner, in his first over from the Nursery End, had last man Peter Chase lbw to claim his third wicket in seven championship appearances.