Owais Shah and Eoin Morgan followed in team-mate Andrew Strauss's first-day footsteps as Middlesex piled the misery on Northamptonshire at Wantage Road.
Shah took his overnight tally to 114 while Irish left-hander Morgan hit an unbeaten 136 as the visitors amassed a superb 545-7 declared.
England spinner Monty Panesar was the pick of the Northants attack, snaring 5-143 before they stuttered in reply.
The hosts finished day two 128-3, still over 400 runs behind Middlesex.
Strauss's anger at being dragged off on Wednesday night in fading light was vindicated early in the morning when he was snared by Panesar five short of his career-best 177.
But Shah and Morgan took up the attack, piling on 102 for the fourth wicket before the former was stumped dancing down the wicket to Panesar.
Morgan went on the attack thereafter and even though wickets fell around him, he bludgeoned Middlesex to a daunting target.
In reply, Middlesex got the perfect possible start to the innings when Tim Murtagh claimed his 62nd championship wicket of the season by trapping Stephen Peters lbw for four.
The home side responded well through Niall O'Brien and Rob White, but both soon succumbed to the introduction of paceman Steven Finn.
The 19-year-old removed White for 32 before forcing O'Brien into a false shot on 30 to leave David Sales and Wessels stranded on 37 and 24 as they ended the day on 128.
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