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Groves recovered from a crash just seven kilometres from the finish line to take the sprint in impressive fashion ahead of Jonathan Milan (Bahrain Victorious) and Mads Pedersen (Trek-Segafredo).
The Australian’s fall was one of several to scupper the peloton throughout the 172-kilometre journey from Atripalda to Salerno, with former maglia rosa Remco Evenepoel among those caught up in what was his second crash of the day.
A dog without its leash caused his frustrating first, which contributed to the Soudal Quick-Step star crossing over four minutes down but without any GC losses after his second crash came inside the final three kilometres.
Fellow general classification rival Primoz Roglic (Jumbo-Visma), too, took a tumble, as did current overall leader Andreas Leknessund (Team DSM), though neither of them lost time after making their way back to the peloton with seven kilometres to go.
It was then that Groves made his move, having been helped back to the front of the peloton by Alpecin–Deceuninck, with close competition from Jayco-AlUla and Team DSM, and ahead of the crash that would eventually rule Mark Cavendish (Astana Qazaqstan) out of contention just 50 metres from the line.
Leading from the front helped Groves avoid such carnage, and while the 24-year-old had both Milan and Pedersen on his wheel, neither men could match his burst along the barriers.
“I surprised myself, I think, today,” said Groves, who is the second Australian to win a stage at this year's Giro since .
“Everything was going well but I crashed at the roundabout corner at seven kilometres to go.
“Luckily, I put my chain back on fast enough and groups came back together, but it wasn’t very clean, we all got lost.
“The guys did a good job very early and, luckily, I was good enough to be in position with DSM and have the legs to lead out and win.
“It’s a dream. This is the race I’ve been focusing on since November and December. I just want to thank the team, everyone involved, my teammates.
“They believed in me and, after two thirds this week, they delivered me to a win.”
Watch Stage 6 of the Giro d'Italia LIVE tonight on SBS VICELAND and SBS On Demand from 8:45pm (AEST).