The former Everton and Chelsea man struck from range and, despite slipping while taking the shot, his effort deflected into the back of the net to score the winner in the 3-2 triumph in Germany.
Victory now has Villa sitting third in the Champions League table and taken them one step close to the last 16.
Leipzig on the other hand have had a European campaign to forget, with the defeat being their sixth this season.
Six consecutive losses is their worst losing streak in the competition ever, and the longest by a German side overall since Bayer Leverkusen in March 2003, which was seven.
They therefore sit on zero points and will be heading out of the competition with a whimper.
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Villa opened the scoring after just three minutes when John McGinn volleyed in from Ollie Watkins' header inside the box.
Some questionable goalkeeping from Emiliano Martinez allowed Lois Openda score into an empty net and equalise for Leipzig though.
The visitors in Germany restored their lead seven minutes into the second half when Jhon Duran netted a stunning effort from range.
Leipzig equalised again not long after with a crisp volley that flew into the top-left corner.
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However, it was Barkley's goal that decided the match and sends Unai Emery's side home with all three points.
It was the midfielder's first ever Champions League goal and came in his 11th appearance in the competition.
More to follow...