The 32-year-old Queenslander drained a six-foot birdie putt on the fourth playoff hole at the Vintage GC in the Hunter Valley on Sunday to edge out former US collegiate star Marchesani, who had mishit his approach shot with a wedge.
Wood turned pro in 2012 and this was only his second victory on the Australasian Tour, with the other coming at the 2021 Victorian PGA.
"It feels great," said Wood after his triumph at the $800,000 tournament.
"I never really thought I'd never win again but the guys out here are just so good. You have to play really good golf to win.
"I knew if it was going to be a playoff ... I'd lost a few beforehand at pro-ams and tour events but I didn't want to lose this one."
Wood had a stroke of good fortune at what became the final playoff hole when his tee shot bounced off a tree and back into the middle of the fairway.
He took full advantage, rifling a sand wedge pin high and draining the birdie putt.
Fellow Australian Will Florimo was eliminated at the second extra hole after missing the green to the right and then hitting a fiendishly difficult flop shot into a bunker.
Florimo had carded the lowest final round in difficult windy conditions on Sunday - a bogey-free five-under 66.
Wood (68), Marchesani (67) and Florimo completed the 72 holes of regulation at six under par.
Overnight leader Ben Henkel (73) finished a shot outside the playoff in fourth at five under, a shot clear of fellow Australian Cory Crawford (68).
Tournament drawcard and defending champion Lucas Herbert was unable to mount a challenge on the final day.
The LIV Golf star eventually signed for a five-over 76 to be tied for 44th at four over.
"Very, very rusty," said the 29-year-old Herbert, who was playing his first tournament in three months,
"I made some discoveries on the range last night that have been flawed for a while, so that's a positive.
"And I've been sick for half of it so that hasn't helped."
The only two men in the storied history of the NSW Open to have successfully defended the title were all time greats Norman Von Nida and Jim Ferrier.
Next week, the Australasian Tour moves to Nudgee GC for the Queensland PGA.
That will be the last lead-in event before the two biggest men's tournaments on Australian soil - the Australian PGA at Royal Queensland on November 27-30 and the Australian Open - headlined by Rory McIlroy - at Royal Melbourne on December 4-7.
