The Latics were sitting pretty in second spot in Group D with minutes remaining at the DW Stadium but the visitors netted a late winner to completely change the face of the standings with one fixture remaining.
Leon Barnett gave Wigan an early lead when he swept home a missed effort from Jordi Gomez but the Essevee answered late in the first half when Chelsea loanee Thorgan Hazard netted his 11th goal of the season.
It appeared as though the contest was headed for a draw, which would have seen Owen Coyle's men sitting second on the table, but Zulte edged ahead in the 88th minute when Junior Malanda fired home from inside the area.
To qualify for the knockout phase, Wigan will have to beat bottom-placed NK Maribor in Slovenia on December 12 and hope top of the group Rubin Kazan can at least hold Zulte-Waregem to a draw in Belgium.
2013/14 UEFA Europa League - Group D score
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