English players Wayne Rooney, who joined the 100 club, and Michael Owen got themselves on the score sheet as Manchester United re-discovered their scoring form and winning habit.
United manager Alex Ferguson looked concerned at interval after making seven changes to his side in a bid for victory at the DW Stadium, following their mid-week defeat at Turf Moor.
United found it hard going in the first half even though they had plenty of possession.
United almost took the lead in the fourth minute with a swift break, when Nani cut the ball back into the area and Darren Fletcher was the first to react but saw his effort cleared off the line by Titus Bramble.
Three minutes later Paul Scholes hoisted a shot high over the bar following a clever flick from Berbatov after Fletcher had carved out the opening.
Wigan were again on the back foot after 16 minutes when Rooney strode forward but his effort was deflected wide.
Rooney then made time and space in the area only for goalkeeper Chris Kirkland to smother his close-range shot.
United were looking menacing every time they poured forward and Berbatov headed into Kirkland's arms following a cross from Nani four minutes later.
Wigan, however, almost took the lead with their first real attack in the 26th minute.
Jason Koumas showed good skill to work his way to the edge of the penalty area. He tried to curl the ball beyond Ben Foster only for the goalkeeper to react superbly and divert it to safety.
United responded in the 32nd minute and Rooney got away from Bramble only to rattle a shot against Kirkland's legs.
Then Fletcher's effort was cleared in the 39th minute after he had been set-up by Scholes.
Wigan, however, came close to opening the scoring in the 49th minute when Charles N'Zogbia won a free-kick off Patrice Evra early in the second half.
N'Zogbia dusted himself down and and picked out Paul Scharner in the area. He peeled away from his marker only to head narrowly wide of the post.
Antonio Valencia, who was such a cult figure during his time at Wigan, had to endure catcalls and jeers after going to ground in the 54th minute but the Ecuadorian winger was smiling two minutes later when he supplied the cross that led to the opening goal.
Rooney's fine header from the corner lead to his landmark one as well.
With United turning the screw, Berbatov added a second two minutes later.
He started and finished the move cheekily chipping the ball over Kirkland before finding the net with his second touch after Scholes supplied the through ball.
United made it 3-0 in the 65th minute thanks to Rooney's second goal of the game. There was touch of luck about this effort as his shot took a slight deflection off Mario Melchiot to wrong-foot Kirkland after Berbatov had supplied the opening.
It was damage limitation now for Wigan, who had lost at home to Wolves in midweek.
However Owen made it 4-0 to United with his first goal for the club, a cool finish into the corner in the 85th minute after he had been set up by Nani.
Nani had the final word with a superb free-kick in stoppage time from 25 yards that sailed over a stranded Kirkland's head.
