Bolton have not beaten Fulham since 1992, and not all in the Premier League, but looked to be on their way until Duff struck with a rare right-foot shot in the 75th minute to deny Gary Megson's men.
Ivan Klasnic had put the visitors ahead in the 35th minute with one of Bolton's only meaningful shots on target, and the visitors put up a fierce rearguard action for the rest of the game.
Gretar Steinsson, Matt Taylor and Gary Cahill all made goal-line clearances and Jussi Jaaskeleinen made one great save to keep Fulham out, until Duff equalised.
The result means Bolton are still in the relegation zone, but at least they showed more spirit than in some recent displays.
They opened the scoring in the 35th minute with an excellent strike from Klasnic. Steinsson hurled in a long throw from the right, Cahill headed towards Klasnic who turned and shot past Mark Schwarzer in the Fulham goal.
At the other end, Fulham were denied repeatedly. Steinsson headed Erik Nevland's shot off the line, then took the ball off Clint Dempsey's toes and headed away the resulting cross.
Dempsey had a long-range free-kick deflected over and then was denied when his header was cleared off the line by Matt Taylor.
Duff shot through a crowded penalty area but Jaaskeleinen made a good save, which he surpassed moments later when he dived full length across his goal to tip over a thumping 25-yard half-volley from Nevland.
But the keeper was finally beaten in the 75th minute when Zoltan Gera won the ball in midfield and passed it to Nevland, who in turn fed Duff.
The Irishman received the ball with his left foot and then deceived his marker but, using his less favoured right foot, he shot diagonally past Jaaskeleinen into the far corner of goal.
Fulham went all out for the winning goal, with Dempsey shooting over in the closing minutes, while at the other end Steinsson could have stolen three points in the final minute only to head over from a good position.