The striker followed up well as Jack Colback sent a high ball into towards Leeds goalkeeper Rob Green.
Leeds United and Newcastle United meet in a league fixture at Elland Road for the first time since 2003 on Sunday afternoon, in arguably the Championship clash of the weekend.
And Gayle showed a clinical touch when he put Newcastle ahead in just the 23rd minute.
It was Newcastle's eighth straight win in the English second tier, keeping them on course for an immediate return to the Premier League.
The meeting of two of England's fallen giants brought a crowd of 36,0002 to Elland Road - the first time Leeds had sold out a league game in nearly six years.
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Nine minutes after the break, Newcastle doubled their lead and it was Gayle, again, who found the back of the net as he prodded home following a one-two between Anita and Ayoze Perez.
Leeds enter the fray this week looking to make it five wins on the bounce, following a recent resurgence in form for the Yorkshire club.
Ayling's deflected shot spun over the crossbar and the right-back then saw his risky cross turned just wide of the post.
Karl Darlow conceded in calamitous circumstances but, fortunately, when his clearance hit Wood, it ricocheted wide, allowing the Magpies to see out the match, condemning Leeds to their first defeat in six games.