Vardy opened the scoring from the penalty spot at St. James’ Park, slotting home on the half hour after DeAndre Yedlin was penalised for handball in the box.
And England centre half Maguire made it two on 73 minutes, nodding home a James Maddison corner.
The result means Rafa Benítez’s side are still searching for their first Premier League victory of the season.
In an open first period, Newcastle were first to threaten, with Wilfred Ndidi lunging to block Ayoze Pérez’s effort.
There were chances at the other end, too, as Kelechi Iheanacho, Ndidi and Ricard Pereira took aim, with the latter’s low strike forcing Martin Dúbravka to turn it past the post.
United grafted, with Pérez freeing Joselu with a fine through ball. The forward’s extra touch allowed Maguire to slide it and alleviate the danger, though Mo Diamé’s header from Christian Atsu’s centre – which flashed just wide – almost broke the deadlock shortly after.
But 30 minutes in, the visitors found themselves with a golden opportunity to take the lead. Maguire saw his header palmed over by Dúbravka but, after a succession of James Maddison corners, England centre back Maguire saw his hooked effort strike DeAndre Yedlin’s arm. Referee Simon Hooper pointed straight to the spot, and Vardy dispatched the penalty to give his side the advantage.
Five minutes after the break, Hooper again had a decision to make when Pérez was bundled to the floor in the box by Maguire, but the official waved away the protests in front of the Gallowgate End.
Maguire – who was at the heart of much of the afternoon’s key events – then sent a volley well wide of the target as the contest continued apace in a breathless, scrappy manner, with Benítez opting to introduce Jacob Murphy and Yoshinori Muto as they sought a leveller.
But instead, with just over quarter of an hour remaining, Claude Puel’s men snatched their second. Maddison sent over an outswinging corner from the right and Maguire met it, thumping a header past Dúbravka to double their lead.
The Magpies’ best effort of the second period came with just a few minutes to go, as substitute Murphy curled just wide of the upright, but it was too late for the hosts to find a way back into the game on what was a forgettable afternoon at St. James’.
