It was also Villa's first success over the London club in eight league and cup encounters which was sealed with an 85th minute second goal from Gabby Agbonlahor.
It was Knight, however, who took the honours following a dramatic week in which he moved from Fulham in a surprise £3.5million deal.
Knight's goal also meant that he had scored twice for Villa in the space of a week, as he put through his own goal while making his last appearance for the Cottagers last weekend.
Chelsea often demonstrated their class but as usual they struggled at Villa Park despite some tenacious play from the likes of Didier Drogba, John Terry, Alex and Michael Essien.
Manager Jose Mourinho must have had mixed feelings about the outcome as they bombarded Villa in the last 20 minutes in search of the elusive equaliser only to be hit by Agbonlahor's late effort.
The high tempo was always maintained with Villa showing more steel in defence with Knight and Martin Laursen linking up well in the middle and Olof Mellberg never putting a foot wrong at right-back.
In a pulsating start Villa were keen not to be overawed by their illustrious opponents as they demonstrated with several promising attacks, the best of which ended in Petr Cech making a brilliant close-range save from a shot on the turn from Agbonlahor.
Chelsea's response were attempts from Essien and Shaun Wright-Phillips as the Londoners stepped up the pressure. But Villa were in no mood to surrender as they matched Chelsea in every department.
Villa's self-belief was evident as they took the game to Chelsea. Even Drogba could not make much impact against either Laursen or Knight.
Chelsea themselves found themselves defending in depth against the pace of Ashley Young, Luke Moore and Agbonlahor. They revelled in the situation as Chelsea won few friends with their complaints and time-wasting tactics.
Terry, in particular, attracted the wrath of the crowd for his dubious tactics, which on one occasion resulted in the linesman waving for a foul for Villa and the referee deciding in favour of Chelsea.
Two minutes into the second half Villa broke the stalemate when Knight capped a marvellous debut with the opening goal. Cech flipped a Young effort over the bar and from the corner Knight headed home despite an attempt by Ashley Cole to clear off the line.
Chelsea then upped the pace and their heavy artillery forced Villa onto the back foot, with substitute Salomon Kalou wasting their best chance for a late equaliser.
But five minutes from time Young broke clear and his mis-hit shot went straight to Agbonlahor to hammer home Villa's second goal and seal a conclusive and well-deserved victory.