Latics five game unbeaten run against Liverpool ended at the hands of two Luis Suarez strikes and a tap in from Jose Enrique.
It was a rough and tumble style game that saw Ben Watson stretchered down the tunnel in the first half.
Roberto Martinez made no changes going into the game other than on the substitutes bench as Ryo Miyaichi replaced Fraser Fyvie.
The first half started frantically as Liverpool notched up their corner count but couldn't turn it into goals as Ali Al Habsi and his defence remained solid.
Arouna Kone provided the bright spark of the first half for Latics with a shot from range that stung the gloves of the returning Pepe Reina.
Watson provided another chance soon after but fired over the bar from the edge of the area.
On 25 minutes his afternoon was over when he jumped up to challenge Raheem Sterling and landed awkwardly on his ankle.
He at first refused to be stretchered off and was helped off by Latics' medical staff but moments later he was carried down the tunnel.
The first half played out with little to worry about for both sides in what was an enthralling game as each manager's tactics went head-to-head.
Three minutes after the break Liverpool took the lead when Sterling nicked the ball off Maynor Figueroa's foot and advanced down the right into the box.
The tricky winger cut the ball back for Luis Suarez who fired the ball into the roof of the net.
Ten minutes later Liverpool made it 2-0 when Jose Enrique was allowed to run from inside his own half and slide the ball behind Latics' back line into the path of Suarez.
Suarez composed himself as Ali Al Habsi raced out to meet him and slotted the ball into the bottom corner.
Latics had to battle to win control of the game back and just as they looked to be getting back into their rhythm, Liverpool struck again.
Sterling proved the threat as he darted down the right wing and cracked his shot across goal.
Al Habsi parried the ball away but into the path of Enrique who arrived at the back post to tap home for 3-0.
From then on Liverpool simply held back and let Latics control possession with the aim of hitting the visitors on the counter.
Latics came close on a number of occasions with substitute Jordi Gomez firing just over on the edge of the box and Kone battling with the back four to create space.
It is Latics' first away defeat since their trip to Swansea and with Reading visiting the DW Stadium next weekend, Roberto Martinez will be hoping his side can get back to winning ways.