He attacked from a small lead group on the penultimate circuit of the 14.3km twisty city course, leaving rivals Tadej Pogacar, Wout van Aert and Mads Pedersen trailing.
Van der Poel poured on the power and even survived a heart-in-the-mouth moment when he crashed on a greasy corner that left him with a ripped shirt and a damaged shoe.
He calmly remounted and extended his lead to more than a minute in front of huge crowds, many in Dutch colours, and avoided any more late scares as he safely negotiated the 43 tight corners, raising his arms aloft and looking to the skies as he crossed the line in George Square.
The five-time cyclocross world champion is the first Dutchman to win the rainbow jersey on the road since Joop Zoetemelk in 1985.
Belgium's Van Aert had to settle for a fourth world silver medal on the road with Slovenia's two-time Tour de France winner Pogacar outsprinting Pedersen for bronze.
Van der Poel, whose father was a world champion cyclist and whose grandfather Raymond Poulidor won the Vuelta a Espana, is a sporting superstar in the Netherlands but his ride in Glasgow addresses one gap on his glittering palmares.
"Maybe this completes my career, it's maybe the biggest victory on the road and I cannot imagine riding in the rainbows for a year," Van der Poel said.
"When I went away, I didn't expect to have a gap but then when I saw nobody was following it gave me wings and I was just flying around the course. Until the crash.
"For a moment I thought it was over."
PROTESTERS HALT RACE
The 271km race which started in Edinburgh was halted for nearly an hour on the approaches to the Glasgow circuits after protesters from environmental group This Is Rigged blocked the road ahead.
Police eventually removed the protesters, some of whom reportedly glued themselves to the road, and made five arrests.
Before the stoppage, nine riders had formed a breakaway, although none of them were big favourites.
With the Belgians and Danes leading the chase towards Glasgow and the scheduled 10 laps of the circuit, the gap was eroded and they were eventually consumed by the big guns.
The incessant cornering and accelerations decimated the peloton, leaving a select group from which Italian Alberto Bettiol launched an audacious attack with around four circuits remaining and built up a handy lead.
But once Van der Poel, Pogacar, Van Aert and Pedersen organised the chase it was curtains for the Italian and the stage was left for the three biggest names in the sport, along with 2019 world champion Pedersen, to fight for gold.
Heavy rain provided another twist to the plot and on another day Van der Poel might have paid for his spill as he slid across the ground and into a barrier but, with a rainbow arcing over the city, he closed in on gold.
"I was not taking risks, and I don't know in this corner all of a sudden I was on the ground. I was pretty pissed at myself," Van der Poel said. "It was super slippery and really difficult but I managed to pull it off."
When Van der Poel powered up the steep Montrose Road climb for the final time he could finally relax and enjoy ending the long Dutch wait for a road world champion.
He could go for the double in next week's mountain bike race.
