An own-goal from Potters captain, Ryan Shawcross, helped the Latics to a first-half lead which they then built on in the second half.
A quick-fire double from Kal Naismith ended any hopes from Stoke to snatch anything from the fixture.
The dangers of relegation loom both on and off the pitch for Stoke
Players with the names of Jack Butland, Shawcross, Sam Clucas, James McClean, Mame Biram Diouf and Sam Vokes would not normally be associated with the third division of English football but they soon could be. O'Neill shared his frustration with his players repeatedly as they were sloppy and struggled to hold onto possession for large parts of the game.
Stoke are not just in trouble on the pitch, their troubles will get worse financially if they were to drop down to League One. It was only 2018 when Stoke last played in the Premier League which means many players' contracts are still Premier League priced.
The Potters had the most expensive team in the history of the Championship last season with £196 million, which is more than Newcastle United in 2016/17 with a cost of £147 million.
The Netflix documentary 'Sunderland 'Til I Die' highlights similar circumstances to what anyone associated with Stoke could see their team in. Sunderland suffered the double drop to League One whereas this could be Stoke's second relegation in three seasons.
Stoke have paid £9.6 million to sign players and coaches in 2019 which would prove an incredible waste if O'Neill cannot keep his side safe from the dreaded drop to the third division.
Not only do the Potters desperately need points but they are almost at the point where they need results to go their way if they are to stay up. O'Neill has one heck of a challenge on his hands.