"White Noise" is the first of four Netflix-produced films competing for the top prize Golden Lion at the festival as the streamer seeks to bolster its artistic credentials.
US politician Hillary Clinton was among the celebrities walking the red carpet for the opening ceremony of the world's longest-running film festival, which is celebrating 90 years since its first edition.
"White Noise" stars Driver as a Hitler studies professor in a small college town, which experiences an "Airborne Toxic Event" that leaves the community desperate for reliable information -- while his wife (played by Greta Gerwig) has her own struggles with prescription meds.
A sharp and funny satire of US consumer culture and academic navel-gazing, it reunites Driver with director Noah Baumbach following their lauded "Marriage Story".
Though based on a famous Don DeLillo novel from 1985, Baumbach told reporters he "couldn't believe how relevant it felt" when he re-read it in 2020.
Driver said he had great fun playing a character "who was so stressed and doing his best to pretend he wasn't", but joked that he got carried away fattening up to play a middle-aged dad.
"I put on weight and we had a back-up stomach -- and then we didn't need the back-up stomach," he said.
"La Mostra", as the festival is known, takes place each year on the beach-lined Lido island and is well-timed to launch Academy Award campaigns.
Eight of the last 10 Best Director Oscars have gone to films that premiered at Venice, including the most recent winner Jane Campion for "Power of the Dog" -- another Netflix production.
Also gracing the Lido on Wednesday was French actress Catherine Deneuve, who wore a Ukrainian flag pinned to her jacket as she arrived to pick up a lifetime achievement award.
An icon in France since the 1960s, the notoriously frank Deneuve seemed non-plussed by the accolade.
"One doesn't look backwards," the 78-year-old told AFP. "It's not a refusal, it's just that one doesn't have time. I was filming in Paris a few weeks ago and starting a film in English in Belgium in less than a month."
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