The Dutchman won in a suffocating sprint at the top of the final climb to the citadel (3.8 km at 5% average gradient) ahead of the Eritrean Biniam Girmay.
Caleb Ewan, in a good position in the wheel of the latter, fell heavily in the last meters.
After a slow-paced day, everything went as planned in the final kilometers of the 195 km long first stage between Budapest and Visegrad.
After his six days in yellow in July 2021 and his number in Mûr-de-Bretagne to steal the golden tunic from Julian Alaphilippe, Mathieu van der Poel was expected on Friday for his first Giro.
He doubted he could let go of the most agile sprinters in this “not steep enough” final.
And indeed Ewan was still present in the final kilometers but, pushed to his limits, he touched Girmay's wheel.
On the front of the stage since his success in Ghent-Wevelgem at the end of March, the 22-year-old Eritrean, who is participating in his first grand tour, was close to beating MVDP.
The Dutchman crossed the line empty.
Caleb Ewan, one of the best sprinters on the field, got up with a particularly shredded shoulder.
Dutchman Mathieu Van der Poel first pink jersey of the Giro, May 6, 2022 in Visegrad (Hungary) Luca Bettini AFP
Several crashes punctuated the last kilometers without hitting the big favourites.
Main contender for the "trofeo senza fine" after his success in 2019, Ecuadorian Richard Carapaz finished sixth in the stage.
The Spaniard Pello Bilbao, coming out of a convincing Tour of the Alps, took third place in the stage.
© 2022 AFP