Pavel Pogrebnyak had brought the game level following Emmerson Boyce's goal before the Russia international saw his shot hit the bar and then bounce off the line. Pogrebnyak hit the post as Fulham continued to press and then Senderos nodded home John Arne Riise's free-kick.
Clint Dempsey burst down the left flank early in the first half and went down under pressure from Gary Caldwell but referee Lee Mason waved away the penalty appeals. Jordi Gomez fired over, before Damien Duff miscued with the goal gaping. Victor Moses forced Mark Schwarzer into action with a stinging effort in the 12th minute.
Pogrebnyak and Senderos had efforts, before Mousa Dembele saw a fierce drive blocked. Neat interplay between Riise and Dempsey allowed the latter to fire the ball across the face of goal. Wigan striker Franco Di Santo limped off injured and was replaced by Conor Sammon. Duff curled wide and Dempsey forced a low save from Ali Al-Habsi before Gomez forced Schwarzer into a low save.
Six minutes after the restart Gomez controlled and struck into the side netting. Moses tested Schwarzer from long range, before Maynor Figueroa's bouncing effort went well wide. Wigan took the lead in the 57th minute when Boyce followed up his pass to Sammon and hit an exquisitely-struck shot from 20 yards into the bottom left hand corner.
The lead lasted just over 60 seconds as Pogrebnyak hit a left-footed effort past Al-Habsi. The Russia international then hit a shot which hit the underside of the crossbar and bounced down toward the line but the officials ruled it was not a goal. Dempsey forced Al-Habsi to parry and Pogrebnyak's follow-up bobbled onto the post. Senderos got the winner as he headed home Riise's free-kick.