To make matters worse for the leaders, they had skipper Nemanja Vidic sent off for a second bookable offence in stoppage time - meaning he will miss Sunday's trip to Liverpool.
Trailing to Wayne Rooney's fifth goal in as many league games at the break, Chelsea levelled a thrilling encounter when Luiz volleyed home his first goal since a £25million transfer window move from Benfica.
And when Yuri Zhirkov went down under Chris Smalling's challenge in the box 12 minutes from time, Lampard strode up to extended an unbeaten home record against their visitors dating back to 2002.
More importantly, it cut United's advantage over Chelsea - who have a game in hand - to 12 points and open up the possibility of Arsenal closing to within a point if they win their oustanding game against Tottenham.
The annoyance for Sir Alex Ferguson would have been that Luiz appeared fortunate not to have been sent off for tripping Rooney moments before Lampard's winner, having already been booked.
Yet, that was only poetic justice given even the United boss felt his star striker was fortunate not to be banned for his attack on James McCarthy at the DW Stadium on Saturday.
Until he found the net, the 25-year-old's notable involvement of a sustained purple patch for the visitors was to fluff a free header on the edge of the six-yard box.
Then he made the breakthrough. Allowed to creep away from the Chelsea defensive line by John Terry and the otherwise excellent Luiz, Rooney collected Nani's pass with his back to goal and spun round quickly.
Branislav Ivanovic recognised the danger but was powerless to do anything about it as Rooney took aim from 25 yards and beat Petr Cech with a ferocious shot that flew into the bottom corner.
At that stage, United deserved their lead.
Although Chelsea had plenty of possession and Ashley Cole was sarcastically urged to "shoot" by the visiting supporters, Florent Malouda had failed to capitalise on their one opening of note when he drilled a shot from Nicolas Anelka's cross straight at Van der Sar.
The Dutchman's moment of the season was still to come. And it will be talked about long after his retirement at the end of the season.
When he had only been able to push Frank Lampard's long-range free-kick towards Ivanovic, the equaliser looked certain. In fairness to the Serb, the ball did not come towards him at the right height, so he could only bundle the ball rather than strike it.
Still, it was heading over the line until Van der Sar despairingly flung out an arm and somehow managed to push the ball upwards, changing its trajectory so it struck Vidic, who was scrambling back on the line.
Van der Sar then completed mission impossible by clawing the ball away from goal, and dangerous Chelsea feet, so Darren Fletcher could hammer it to safety.
Luiz has thus far proved to be the most astute signing of Chelsea's £75million January purchases, combining solid defensive work with typical South American ability on the ball.
Clearly, he can strike a ball pretty well too as he proved when lashing home a 10-yard volley, from Michael Essien's cross.
Chances came and went with breathtaking regularity at either end. Lampard and substitute Didier Drogba for Chelsea. Rooney for United, drawing frustrated cries from Gary Neville, who was wedged amongst the visiting supporters, cheering for the club he has always loved.
Neville would have presumably taken a pretty dim view of Luiz's blatant trip on Rooney, which would surely have brought a red card had it been spotted by referee Martin Atkinson.
The Yorkshireman missed it, but not Chris Smalling blocking off Yuri Zhirkov at the other end moments later, allowing Lampard to smash home his penalty.
Zhirkov came agonisingly close to grabbing a third goal when his fierce shot struck Vidic and crashed against the post.
Vidic's evening was to end on a sour note though as suddenly United look vulnerable ahead of their Anfield trip.