Remco Evenepoel suffered a fractured pelvis crashing off a bridge during the Il Lombardia race.
The Deceuninck-Quick Step rider, 20, was part of a leading group who were descending from the Colma di Sormano - the highest climb on the race.
He was lying around fourth in the group when he struck the wall of a bridge before somersaulting on to his back and over the edge.
Evenepoel was attended to by paramedics and taken to hospital.
In a statement his team said he had suffered "multiple injuries".
"Evenepoel crashed inside the last 50 kilometre hitting a bridge wall and going over it into a ravine," Deceuninck-Quick Step said.
"Remco was conscious at all times as he underwent a series of examinations to reveal the extent of his injury.
"Unfortunately, the X-rays showed a fractured pelvis and a right lung contusion, which will keep Evenepoel on the sidelines for the upcoming period.
"He had a quiet night at the hospital and the evolution of his condition is good. Due to the nature of the injury, Remco has to be transported by plane to Belgium in a supine position [lying down].
"The team is doing everything possible to bring him back home as soon as possible, hopefully in the next 24 hours, in the most efficient and safe way."
The Belgian is one of the most promising prospects in road cycling, winning the Tour of Poland and the Volta a Burgos already this year.
He is being compared to Eddy Merckx - a fellow Belgian widely regarded as the greatest cyclist of all time - for his all-round ability on the bike.
The one-day 'monument' race from Bergamo to Como was won by Jakob Fuglsang of Astana after breaking away from Jumbo-Visma's George Bennett - himself in good form after winning the Gran Piemont one-day race in Italy last week.
They were in a breakaway with multiple Grand Tour winner Vincenzo Nibali and last year's Il Lombardia victor Bauke Mollema, both of Trek-Segafredo.
In another bizarre twist at the end of the race Bora-Hansgrohe's Max Schachmann was struck by a car which somehow entered the closed roads and cut across the German Paris-Nice winner as it attempted to park.
Quick Step's second horrifying injury in a week
The Tour of Poland was also the race where Evenepoel's team-mate Fabio Jakobsen last week suffered a huge crash in a bunch sprint on the first stage.
Jakobsen was hospitalised and put into an induced coma as well as having plastic surgery to his face.
The crash was caused when Jumbo-Visma's Dylan Groenewegen leaned toward Jakobsen, causing him to be pitched into barriers which broke and saw the sprinter strike a post and a spectator, who also needed hospital treatment.
It prompted an angry reaction, leading Jakobsen's team boss to call for Groenewegen to be jailed.
Jakobsen has since been transferred to hospital in his native Netherlands to continue his recovery.
Il Lombardia result:
1. Jakob Fuglsang (Den/Astana) 5hrs 32mins 54secs
2. George Bennett (NZ/Jumbo-Visma) +31secs
3. Aleksandr Vlasov (Rus/Astana) +51secs
4. Bauke Mollema (Ned/Trek-Segafredo) +1min 19secs
5. Giulio Ciccone (Ita/Trek-Segafredo) +1min 40secs
6. Vincenzo Nibali (Ita/Trek-Segafredo) +3min 31secs
7. Max Schachmann (Ger/Bora-Hansgrohe) +4mins 31secs
8. Diego Ulissi (Ita/UAE Team Emirates) +5mins 20secs
9. Ben Hermans (Bel/Israel Start-Up Nation) +6mins
10. Mathieu van der Poel (Ned/Alpecin-Fenix) +6mins 28secs