The in-form Bundesliga outfit, who suffered a harsh 4-1 loss at Goodison Park, were on top for long periods at the Volkswagen Arena, but they were expertly unpicked on the break in each half.
Romelu Lukaku opened the scoring two minutes before half-time on the end of Kevin Mirallas' pass and roles were reversed as the striker's Belgium international colleague sealed the points in the 75th minute.
An earlier 1-1 draw between group counterparts Krasnodar and Lille meant Everton were guaranteed a place in the knockout stages, but manager Roberto Martinez can now reflect on securing top spot with an impressive scalp.
Wolfsburg, second in the Bundesliga, will join them in going through if they avoid defeat at Lille in the final group match, although their progress might have already been assured had the impressive Ivan Perisic not seen a 22nd-minute effort wrongly disallowed for offside.
Perisic flashed a volley across the face of goal in the second minute and the same player hooked into the side netting when Kevin De Bruyne's clever throughball caught out Tony Hibbert.
Sylvain Distin should have put Everton in front in the 13th minute when he headed Luke Garbutt's corner into the turf and home goalkeeper Diego Benaglio tipped onto his crossbar.
The hosts sprung up the other end on the counter attack and, from a corner of their own, Tim Howard brilliantly kept out Aaron Hunt's first-time strike.
Perisic and his team-mates were understandably frustrated in the 22nd minute as the Croatia international netted from Nicklas Bendtner's flick, only to be incorrectly ruled offside.
Everton midfielder James McCarthy suffered a recurrence of his recent injury problems in the 30th minute, hobbling off with an apparent hamstring complaint to be replaced by Leon Osman - the Merseyside team's weekend matchwinner against West Ham.
Wolfsburg continued to dominate, but after Phil Jagielka made a superb block to deny De Bruyne, they left themselves exposed from an attacking corner and Everton took advantage clinically.
Mirallas touched the ball on to Lukaku, who outmuscled Naldo following a poor first touch to race clear and fire the visitors in front.
Hunt thudded a left-footed drive into Howard's arms eight minutes into the second period as Wolfsburg pressed forward but struggled to regain their earlier rhythm.
The offside flag denied them once again - justifiably this time - in the 55th minute when Bendtner nodded in from a De Bruyne corner before Aiden McGeady spurned a glorious chance to double Everton's advantage.
Osman released Lukaku down the left channel and his shot was beaten into McGeady's path by Benaglio but the Republic of Ireland international mishit the rebound over.
Perisic carried the charge for Wolfsburg once more, cutting in from the left flank and striking the outside of the near post with Howard beaten.
Howard and Jagielka took turns to thwart Perisic and the former did well to palm away Marcel Schafer's swerving long-ranger.
The United States goalkeeper and his defensive colleagues could breathe easily once Lukaku gave another demonstration of his brute strength to feed Mirallas, who sauntered past Luis Gustavo to finish.
Substitute Maximilian Arnold struck the post in the final minute to sum up Wolfsburg's night before a linesman's flag prevented Everton replacement Ross Barkley from adding undue gloss to the scoreline.
