Villa were without injured striker John Carew, while Nicky Shorey returned at left-back to allow Gareth Barry to revert to his preferred midfield berth.
The home side made a strong start to the game and were rewarded for their efforts with the opening goal after eight minutes, as Martin Laursen rose to head Ashley Young's corner from the left into the back of the net.
Ajax were already under the cosh at this stage and continued to be pegged back, as Martin O'Neill's side piled on the pressure.
However, the Dutch side silenced Villa Park 22 minutes in as Urby Emanuelson's whipped corner from the right was met by Thomas Vermaelen, who powered his header over Brad Friedel.
Ajax then threatened from another corner shortly before the half-hour mark, with skipper Klaas-Jan Huntelaar almost converting at the far post.
Ten minutes before the interval a James Milner cross from the right reached Ashley Young, but he scuffed his shot a couple of yards wide of the upright.
Right on the stroke of half-time Villa regained their lead, as Ashley Young got away down the left and his pull-back eventually reached Barry, who calmly sidefooted home from 15 yards out.
After the interval Villa maintained the impetus they gained from Barry's strike and went in search of a third goal.
However, they were unable to fashion any clear chances as the hour mark approached.
Gabriel Agbonlahor had an appeal for a penalty waived away as Villa remained on top, before the tempo of the game started to drop a little.
Huntelaar had a free-kick deflected narrowly over the top to fire a warning to the home side, before Friedel had to get down smartly to turn aside Emanuelson's 25-yard left-foot effort.
But Villa stood firm and safely saw out the remaining minutes to start their Group F campaign with a valuable victory.