Wigan gave a polished display to clinch their sixth successive Premiership win and leave Portsmouth still looking for a first home victory of the season.
Pascal Chimbonda rose above a static Portsmouth defence to head Wigan in front at the start of the second half.
Chimbonda turned provider as Wigan caught Portsmouth on the break, crossing for Jason Roberts to tap home.
Dario Silva's header on to the roof of the net was the closest Pompey came to adding to their three home goals.
Portsmouth were given a boost by the return on the bench of striker Lomana Lua Lua six weeks after contracting malaria.
Silva embarrassed Wigan keeper John Filan and almost headed Pompey into an early lead when he got to Gregory Vignal's long ball ahead of the Australian, but his brave header looped over the bar and on to the roof of the net.
Despite home advantage Pompey boss Alain Perrin again saddled Silva with a lone-striker's role with Zvonimir Vukic tucked in just behind.
With Silva as their sole forward outlet, Portsmouth were in danger of surrendering the initiative to Wigan's tidy football and Gary O'Neil wasted a rare sight of goal by slamming a 20-yard free-kick into the defensive wall.
Wigan made their intent clear from the start of the second half when Damien Francis saw his shot deflected wide.
Chimbonda rises highest to head Wigan in front
But from the resulting corner Wigan took the lead when Jimmy Bullard's well-flighted corner found Chimbonda rising above a static Brian Priske to head powerfully home.
Pompey almost sprang an instant reply when Vukic's corner came off Stephane Henchoz's head and flashed across the face of goal.
Wigan should have stretched their lead when Graham Kavanagh spearheaded a swift break but with team-mates waiting the midfielder wasted the opportunity by going alone and shooting wide.
Laurent Robert was introduced to a smattering of boos from the home fans following the incident at Sunderland last week.
But he immediately whipped in a good cross which cried out for a blue shirt to attack it and when presented with a free-kick in a promising position he drove it straight into the wall.
Lua Lua's well received introduction was in marked contrast to Robert's but even his trickery struggled to make an impression on Wigan's solid defence.
Wigan sealed the points with a stunning break as Chimbonda broke up a Pompey attack, and raced down the right flank to take a return pass from Henri Camara before sprinting clear to roll the ball across the face of goal for Roberts to tap in.
Portsmouth manager Alain Perrin:
"You have to take the example of Wigan, you must play well in defence and know when to counter.
"It is difficult for the confidence of the players because they badly want to give a win to the fans. But sometimes they attack too much and don't defend.
"We just have to play better if we want to win. It was not a good day."
Wigan boss Paul Jewell:
"We are 25 points closer to safety that is all. We know we're doing well but we won't get carried away.
"Winning breeds confidence but we're not getting over-excited because the next game is at home to Arsenal and we have a tricky little run coming up.
"But when we prepare for a game we will always prepare to win it."
Portsmouth: Ashdown, Primus, Priske, Stefanovic, Griffin (Diao 76), O'Neil, Hughes, Taylor, Vignal (Robert 60), Silva, Vukic (LuaLua 68).
Subs Not Used: Westerveld, Mbesuma.
Wigan: Filan, Chimbonda, Henchoz, De Zeeuw, Baines, Bullard, Francis, Kavanagh, McCulloch, Camara (Taylor 89), Roberts (Jackson 88).
Subs Not Used: McMillan, Pollitt, Mahon.
Booked: Francis, De Zeeuw.
Goals: Chimbonda 48, Roberts 79.
Ref: M Clattenburg (Co Durham).