The win was Pompey's fifth in six games in all competitions and the FA Cup favourites are looking in top form at the moment.
Harry Redknapp claimed earlier in the week that his Pompey side were still trying to finish in the top five and you cannot discount that.
Redknapp warned his team they must forget about FA Cup glory and concentrate on the league and they seemed to take his word for it.
Portsmouth started brightly and Milan Baros teed up Hermann Hreidarsson, who hit a fierce 15-yard piledriver which Chris Kirkland just managed to claw away for a corner.
Niko Kranjcar then went close with a 22-yard free-kick that whistled just past the right-hand post.
Defoe should have broken the deadlock in the 12th minute but blazed a ten-yard effort over the bar.
Pompey were almost made to pay straight away when Wigan flew up the other end and Antonio Valencia was played in.
His shot beat David James, but not Glen Johnson who dived in to toe-end the ball against the bar from half a yard out to save a certain goal.
Pompey took the lead through Defoe's seventh goal in seven games since joining the south coast club in the 32nd minute.
John Utaka beat three players and his shot was blocked by Kevin Kilbane and fell to Defoe, who slid the ball home left-footed from an acute angle
Defoe has now scored in Portsmouth's last five games at Fratton Park to better Alan Biley's 25-year-old record of four in the 1982/83 season.
Kilbane went close for Wigan just before the break as Portsmouth's fans went into party mode at the thought of a first visit to the new Wembley.
The Republic of Ireland international hit his shot just wide of the right-hand post.
Baros could have settled the game just after the break but dallied over a shot and the danger was cleared.
The Czech international still has not scored in seven appearances since joining on loan from Lyon.
Utaka then went close with a 20-yard shot after a mazy dribble past two defenders.
Wigan were given a totally unwarranted penalty on the 63rd minute when Valencia fell over under Sylvain Distin's challenge and referee Alan Wiley pointed to the spot.
Taylor took the penalty, but James saved and Taylor blasted the rebound over the crossbar.
Defoe added a late second when he latched onto Kranjcar's pass and sprung the offside trap.
The England striker ran through to finish past Kirkland in the fourth minute of injury time.