The veteran inherited the lead early in the race thanks to a spectacular engine fire for Cam Waters, before withstanding intense, race-long pressure from Broc Feeney.
The win was Winterbottom's first since Pukekohe 2016 and first podium since Wanneroo in 2018.
It is also Team 18's first win in Supercars.
"I'm emotional," said Winterbottom. "That's awesome. I told [team owner] Charlie [Schwerkolt] when I joined that we were going to try and win, and far out, it's taken a while.
"That was hard work, that was really hard work. That's awesome, I'm pumped."
Waters made a solid start from pole, using the inside line to run Broc Feeney wide around the long first corner.
That opened the door for Mark Winterbottom to sneak past Feeney and grab second place.
Waters looked to quickly settle into the lead, only for his charge to come to a fiery halt at the beginning of the fifth lap. That was when his Tickford Mustang went up in flames, marking the third serious fire since the Gen3 cars were introduced at the start of the season.
The subsequent safety car led to the entire field diving into the pits, Winterbottom managing to resume with his newly-inherited lead over Feeney intact.
The frantic round of stops also worked well for Will Davison, who emerged in third place ahead of Bryce Fullwood.
The veteran continued to lead Feeney across what became a long second stint, before a second fire – this time a grass fire lit by Declan Fraser's spinning Mustang – prompted a second safety car on lap 16.
Once again Winterbottom held his nerve at the restart, but was unable to shake a determined Feeney as the laps wore on.
The gap was never over a second, Feeney's pressure relentless as he chased Winterbottom to the flag.
However the second-year driver couldn't find a way through, Winterbottom holding on to break his six-year winless streak.
Davison came home third for Dick Johnson Racing, while Brodie Kostecki ran down Fullwood with five laps to go to grab fourth.
Shane van Gisbergen ran fourth early in the race but struggled after his stop and slipped back to sixth.
Will Brown was seventh, right behind van Gisbergen, while Chaz Mostert was under Brown's rear wing in eighth.
Anton De Pasquale finished ninth and Tim Slade 10th.
Kostecki continues to lead the standings with a 103-point margin over Brown and 179 points over Feeney.
The Darwin Triple Crown continues with two qualifying sessions and two more 100-kilometre races tomorrow.
