Hull moved further clear of the Championship relegation places as they consigned bottom side Wigan to a fourth straight defeat.
The Tigers took a deserved half-time lead thanks to Jacob Greaves who lashed a fine finish into the far corner following Jean Michael Seri's corner.
The hosts levelled with their first effort on target just after the hour when substitute Nathan Broadhead muscled his way through to head in James McClean's near-post corner.
However, Oscar Estupinan's scuffed finish trickled across the line to restore the lead before Tyler Smith's late double condemned Wigan to a third successive 4-1 defeat.