Dropped England paceman Steven Finn claimed 4-46 as Middlesex dismissed Durham for 143 at Lord's then limped to 126-5 at stumps.
Middlesex, starting their reply at 3.40pm after an early tea break, saw Joe Denly (nought) fend at a short one from Graham Onions that he might have left alone and nick to second slip to give Onions his 400th first-class wicket.
Sam Robson (one) lost his off stump after aiming to drive against Chris Rushworth, Adam Voges cut an Onions long-hop to cover point to go for nine, then, Eoin Morgan (20), off balance and working to leg, departed lbw to an in-swinging yorker from Ben Stokes.
In the final hour, John Simpson (20) clipped off his legs straight to Mark Stoneman at short mid-wicket, but Neil Dexter (40 not out) and Gareth Berg (28 not out) survived as common sense finally prevailed.
Durham's batting demise started from the second ball of the match when opening bat Stoneman (two) sparred at a Tim Murtagh leg-cutter to edge to wicketkeeper John Simpson.
Three overs later, Scott Borthwick (four) feathered one from Corey Collymore into the gloves of Simpson then, four runs on, Keaton Jennings (three) held his bat out to dry against Murtagh for Simpson to snaffle the third of his five catches.
Stokes launched a counter-attack against the swinging ball hitting four boundaries - including a couple of rasping cover drives - in a brief cameo stay of 21 that ended with the introduction of Finn.
With National selector Geoff Miller as well as one-day coach and co-selector Ashley Giles watching and taking note, Finn made an immediate impact by having Stokes caught low down at third slip by Robson.
Chasing their first win at Lord's since 1998 - their sole championship success at the home of cricket - Durham re-grouped briefly until Will Smith (24) chased a wide one from Berg to edge to second slip in the over before lunch.
Having gone in at lunch on 74-5, Durham's slide continued five overs after the resumption when left-handed Phil Mustard launched at a wide drive against Berg only to gift Simpson his fourth catch of the innings with the total on 93-6.
Mark Richardson helped add 19 for the seventh wicket before Paul Collingwood, working to leg against a short one from Finn, found a leading edge to loop a simple return catch to the bowler.
In the next over, Richardson (nine) aimed to pull a leg-side long-hop from Collymore only to edge through to Simpson, leaving Finn to polish off the tail by snaring Onions (four) leg before and having Rushworth (five) held at mid-on.