Latics were hoping to win their ninth straight game in all competitions - which would have been a new benchmark since they entered the Football League in 1978 - and, after Jordi Gomez had a penalty saved by Marek Stech in a flat first half at the DW Stadium on Tuesday night, Nick Powell nodded them ahead just after the break.
However, after 82 minutes, Ishmael Miller turned the game on its head with a three-minute left-footed brace to put the visitors ahead.
Wigan came back, James McArthur levelling, before Byron Webster's own goal put Uwe Rosler's men ahead with just two minutes to go.
However, with goalkeeper Stech up for a corner, Luke Ayling bundled home in the fourth minute of stoppage time in the final act of those mad final stages.
Before the game, boss Rosler claimed he know all about Yeovil, having been Brentford manager when they defeated them in the League One play-off final last May. He warned it may take some time for his men to open up the stubborn Glovers but, 25 minutes in, they had the ultimate chance to break the deadlock.
Gomez's deep corner was heading for Powell, who jumped and spun to the turf with Matteo Lanzoni's arms on his back, and referee Andy D'Urso awarded an instant penalty.
It appeared a soft call and Yeovil felt justice was served when Gomez failed to replicate his spot-kick goals against Manchester City and Sheffield Wednesday this month as Stech guessed right and pawed the ball away to his left.
Latics' woes were soon compounded as James Perch, struggling from an earlier challenge with team-mate Callum McManaman, had to be replaced by Thomas Rogne two minutes later.
Wigan looked to quickly shake off the disappointment of Gomez's miss, McManaman firing into Stech's arms and Nicky Maynard drilling wide, yet they were largely flat in the opening 45 minutes.
Rosler's half-time words clearly had a galvanising effect, though. Jean Beausejour went close with a smash across goal while McArthur's long-range try ended up in Stech's gloves before Powell headed home a poacher's effort nine minutes into the second period.
The hosts broke at pace and after McManaman's cross had been steered towards the back post by McArthur, Powell nodded in from barely three yards out. Fittingly, he got the wrong side of Lanzoni to do so and, on just his second Yeovil start, the ex-Oldham defender appealed in vain for an offside call which never looked like coming.
But just eight minutes later, Gary Johnson's men should have been level. Tom Lawrence swung a teasing across over the six-yard box and Miller somehow failed to get the connection needed on his close-range header.
On a night when the strugglers' chances were sparse, that miss looked all the more costly as Wigan pushed for a second goal.
But the 27-year-old would kick off a thrilling finale by twice bending into the far corner with his left foot.
The striker ran the length of the pitch to celebration the moments of pure jubilation - but Wigan were far from done.
The hosts equalised through McArthur's finish as he slotted home Beausejour's cross. Less than two minutes later they were ahead, another Beausejour centre headed into his own net by Webster.
If those six minutes had shown anything, though, it was that this was going to be far from straightforward for Wigan and, in the fourth-minute of stoppage time, Yeovil would grab an equaliser their efforts would warrant.
Stech caused problems from Lawrence's corner and Ayling poked the ball in from close range to close an enthralling contest.