Premier League basement boys Pompey started the better of the two teams and carved out an early chance, when Frederic Piquionne forced a good save out of Cottagers goalkeeper Mark Schwarzer.
Fulham meanwhile were playing like a team that had lost their last five games. Low on confidence, they were guilty of giving the ball away cheaply though they did create the best chance of the game just after the half hour.
Bobby Zamora's cross was headed back by Jonathan Greening and Stefano Okaka, making his debut after signing on loan from Roma, somehow headed wide from a yard out.
Roy Hodgson's men improved after the break, with Damien Duff at the heart of much of their good play. Twice Duff put in a great cross for Bobby Zamora, but the former Spurs striker couldn't find a way past David James.
But just when the game looked like heading for a goalless draw, the Cottagers took the lead with 16 minutes remaining. Duff got free on the right and crossed towards Zamora, who looked in an offside position, but the ball deflected into the path of Jonathan Greening, who coolly slotted home from 12 yards.
Pompey boss Avram Grant threw on new striker Quincy Owusu-Abeyie as they tried to get back into the game, but they failed to create another chance as Fulham held on for their first league win since beating Manchester United just before Christmas.