Shane Snater took two wickets in as many balls to end Middlesex's stubborn resistance and wrap up Essex's first LV= Insurance County Championship win at Lord's since 2009.
Chasing a target of 308, the home side displayed fighting spirit on the final morning as Ryan Higgins and Luke Hollman frustrated the bowlers with an eighth-wicket partnership of 87.
But Snater finally achieved the breakthrough, removing Higgins and Toby Roland-Jones with successive deliveries after lunch before Jamie Porter collected the final wicket to dismiss Middlesex for 210 and clinch a 97-run success.
Porter and fellow seamer Sam Cook finished with three wickets apiece, while Snater returned figures of two for 34. Hollman top-scored for Middlesex with an unbeaten 63 that included eight boundaries.
Having resumed at 77 for five, the home side lost their sixth wicket in the second over of the day, a rising delivery from Cook that nightwatch Tom Helm could only fend into the hands of first slip.
It was Porter, with six wickets to his name in the first innings, who prised out Stephen Eskinazi, trapping the right-hander in front of his stumps for 37.
But Essex were held up by the eighth-wicket pair, with Higgins largely adopting a watchful approach - although he opted to take on Simon Harmer, pumping the leg-spinner over the rope at long on to lift the total into three figures.
Hollman, meanwhile, looked strong off the back foot as he punched both Cook and Harmer through point to the boundary, along with an audacious reverse sweep off the latter that brought him four more.
The pair shepherded Middlesex to lunch at 162 for seven and they continued to hold out for another half-hour after the resumption, when Snater finally gained tangible reward for his consistent spell.
Higgins, whose edge had fallen short of the fielder in Snater's previous over, was leg before for 41 and Roland-Jones steered the next delivery to first slip, where Alastair Cook leapt to his right to take the catch.
There was still time for Hollman to complete a well-deserved half-century - the fifth of his first-class career - by sweeping Harmer for three before Porter castled Tim Murtagh to seal Essex's victory.
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