Both sides finished with ten men in a thriller at Prenton Park as Wigan stayed top of division two with their third victory on tour as Tranmere suffered their first home reverse.
Wigan went ahead with a penalty in the 53rd minute. Ian Sharps conceded it for a trip on Andy Liddell. The Wigan man retaliated by striking Sharps and was immediately shown the red card.
Naithan Ellington stayed calm to fire home the penalty straight into the centre of the goal as keeper John Achterberg dived to his right.
The ten-man visitors increased their lead in the 67th minute. Ellington was again the marksman with a close-range effort from an angled header by Lee McCulloch.
The Mersysiders then threw everything at Wigan but were themselves down to ten men in the 76th minute. Former Wigan man Simon Haworth went off for his second yellow card for a foul on Paul Mitchell after earlier being cautioned for dissent.
Mickey Mellon and Stuart Barlow fired wide from good openings. Barlow then had a shot kicked off the line in the 86th minute after Ryan Taylor hit a post with a 20-yard free-kick.
Then with time running out athletic keeper John Filan tipped over an excellent effort by Mellon. The home skipper worked tirelessly. McCulloch, Jason De Vos and Ellington were best for the winners.
Said Ellington: "I was very pleased to get the goals but more importantly we have got the win. I had to take the penalty with Liddell being sent off."
Wigan manager Paul Jewell added: "It was a typical derby game but it was an important win for us. There was hard work and determination in abundance and we showed bags of spirit.
"It was a stonewall penalty but my player then raised his hand. There was no malice in it but he got sent off."
Tranmere manager Ray Mathias commented: "It was an unfortunate penalty to concede at a vital stage and the second goal was a killer blow."