The 20-year-old England midfielder went into the game with a question mark hanging over him after a disappointing run of form.
However, he scored twice in the second half as the Black Cats came from behind to win for the first time in 10 Premier League games and plunge Wigan back into trouble.
Mohamed Diame had given the visitors hope of building upon last week's 3-1 win at Blackpool, which lifted them out of the relegation zone for the first time in three months, when he blasted them in front seven minutes after the break.
However, Asamoah Gyan levelled with a close-range header three minutes later and the Black Cats took complete control as they visibly grew in confidence despite losing Phil Bardsley, Danny Welbeck and, within nine minutes of his goal, Gyan through injury.
Henderson gave them a 66th-minute lead and after Stephane Sessegnon has scored his first goal for the club from the penalty spot seven minutes later, added a second to ease the home side home in front of a crowd of 39,650.
It was just what manager Steve Bruce, who claimed a first win over his former club, needed in the 500th league game of his managerial career, although it came at a cost with Welbeck and Gyan joining Fraizer Campbell on the injured list.
Bruce went into the game bemoaning the injury list he believes is the root cause of their recent slump.
By the time the 26th minute had elapsed, the casualty count had increased once again.
Full-back Bardsley was carried off the field on a stretcher having been given oxygen and taken straight to hospital after an early clash of heads with team-mate Nedum Onuoha.
Anton Ferdinand took his place as Bruce was forced to make an early substitution for the third successive home game.
But if there was no legislating for Bardsley's misfortune, Welbeck's departure was depressingly predictable with the striker having spent the last week battling a hamstring problem before being declared fit to start.
Welbeck has scuffed a second-minute shot straight at keeper Ali Al Habsi and Gyan headed wide from an Ahmed Elmohamady cross.
The best chance of the half went Wigan's way when, with 31 minutes gone, Ben Watson robbed Lee Cattermole deep inside the Sunderland half and the ball ran to striker Hugo Rodallega.
The Colombian thumped a rising shot towards goal, where keeper Simon Mignolet, who endured a difficult afternoon at Birmingham last weekend, made an important save.
Charles N'Zogbia, a long-time target for Bruce, saw a late drive blocked after he cut inside from the right.
Diame, who had scored in the corresponding fixture last season, put Wigan ahead.
The midfielder accepted N'Zogbia's pass and turned expertly past Michael Turner before smashing a 25-yard drive past Mignolet.
The lead last just three minutes as the Black Cats got themselves back into the game.
Henderson took a short free-kick but when the ball was eventually fed out to substitute Steed Malbranque on the right, he cut inside before crossing.
The Frenchman's ball was perfectly weighted for Gyan to rise and power home a close-range header.
But Gyan's joy was shortlived as he left the field on a stretcher within nine minutes having pulled up clutching his hamstring.
The resulting reshuffle saw Sessegnon pushed up front, but it was local boy Henderson who fired his side in front for the first time when he controlled substitute Sulley Muntari's cross on his chest before drilling a left-foot half-volley into the top corner.
Sessegnon got his big chance with 17 minutes remaining when he was barged to the ground by defender Antolin Alcaraz inside the penalty area and referee Lee Probert pointed to the spot.
The Benin international sent Al Habsi the wrong way to wrap up the win, although he was not finished for the afternoon.
Four minutes later, it was he who picked out Henderson in space inside the box and the youngster finished with aplomb once again.
Substitute Franco di Santo's last-minute strike provided little consolation.