Gavin Millar bagged two goals and won a match-clinching penalty as Kilwinning claimed three Premier points and the North Ayrshire derby bragging rights.
The wing wizard's first-half double put the visitors in the driving seat at Meadow Park.
A sensational Jamie Martin volley gave the hosts hope of staging a second half comeback.
But Millar had the last word, drawing a foul from Medda centre-half Neil Slooves to earn Buffs a 75th minute spot kick which David Syme duly converted.
The penalty award undoubtedly fell in the soft category, but once the dust settles, Meadow will probably look back on a poor opening 45 minutes as their undoing.
They fell behind in 16 minutes when Jordan Stuart's searching ball over the top sent Millar racing into the right side of the Meadow box and he kept his cool to slip the ball past goalkeeper Marc Waters from a tight angle.
Millar was back on the scoresheet two minutes later, slamming home a loose ball from eight yards with the Meadow defence at sixes and sevens.
Kilwinning had Meadow exactly where they wanted them and they simply refused to let them get going as an attacking force, exerting complete control over their old rivals.
It was almost 3-0 just after the half-hour mark when Stuart sneaked around the back of the Medda defence at a corner kick but his header flew past the post.
Meadow's first shot on target came on the stroke of half-time but Andy McLaughlin's effort from 25 yards lacked the power and direction to trouble Buffs goalie Jamie Barclay.
As poor as the home side had been, they were back in the match within two minutes of the restart thanks to a moment of magic from Martin.
Brian Connor's mis-hit shot flicked up off the boot of Buffs' midfielder Ricky Hanvey and Martin reacted instinctively, swivelling with his back to goal to smash a superb volley into the top corner from 12 yards.
The goal galvanised the home side and Connor had a chance to level matters in 62 minutes when Boyd slipped him in behind only for Barclay to save with his feet to keep Kilwinning in front.
Chances at the other end were at a premium although David Syme went close with a header that just cleared the crossbar in 69 minutes.
It was then Miller's time to take centre stage again and deliver a killer blow to Meadow.
The former East Kilbride ace drove into the penalty area from the left flank and tumbled to the ground after a coming together with Slooves.
Referee Sean Henderson felt Slooves was the guilty party and pointed to the spot much to the disgust of the home bench and supporters.
Syme assumed penalty kick duties, firing the ball into the corner of the net beyond Waters' reach to restore Buffs' two goal advantage.
Meadow struggled to recover from the setback with Kilwinning seeing out the final 15 minutes in relative comfort to end a run of five Saturdays without a victory.
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