Hughes dived headlong to steer home a speculative free-kick from John Salako on 68 minutes - and that was enough to clinch all three points for Reading.
And Wigan's day went from bad to worse in stoppage time when keeper John Filan was sent off for handling outside his area - though he furiously protested his innocence as he reluctantly left the pitch.
But Reading's victory had looked unlikely for long spells as Wigan, whose only previous two defeats this season have come away from home, looked in control throughout the first half.
Wigan were solid and unfussy and the home side rarely found a way through the Latics' well-organised defensive lines, while Paul Jewell's league leaders always looked a threat on the break.
Geoff Horsfield should have done better than to toe-poke wide after spinning clear of Reading captain Adie Williams in the penalty area.
The impressive Lee McCulloch made the chance with a neat flicked header and McCulloch himself went close midway through the first half with a pot-shot that flew just over from the edge of the penalty area.
But the best chance of the first half fell to defender Ian Breckin seven minutes before the break when Andy Liddell teed him up in front of goal only for the centre back to sidefoot wide with the goal at his mercy.
The home side, who themselves have now lost only twice in seven games under new boss Steve Coppell, looked nervy and disjointed, not helped by losing centre back Williams through injury after only 27 minutes.
Striker Nicky Forster carried their chief threat, but was restricted to long-range shots as Wigan kept him on a tight leash.
And when the former England Under-21 star did escape seven minutes after half time - the striker left in the clear after Matt Jackson completely missed an Ivar Ingimarsson clearance - he shot straight at Wigan keeper Filan.
But the chance signalled a shift in the balance of power and the game swung Reading's way courtesy of Hughes' third goal of the season on 68 minutes.
Salako's free-kick was from only ten yards inside the Wigan half but was dropped perfectly into space for Hughes, who threw himself in to guide a header beyond Filan's grasp.
Wigan threw everything forward in search of a way back, but when Filan handled under pressure from Forster in the dying seconds, the damage was complete.