British rider Geoghegan Hart (Ineos Grenadiers), who won the Giro in 2020, was riding with his team-mates including overall leader Geraint Thomas, who also hit the deck along with race favourite Primoz Roglic (Jumbo-Visma).
Thomas and Roglic were able to re-join the peloton but Geoghegan Hart, third in the overall standings, was attended to by medics before being carried on a stretcher into an ambulance.
"The Brit will head to hospital for checks and we will have further updates in due course," Ineos Grenadiers said on Twitter.
Shortly afterwards, Movistar rider Oscar Rodriguez suffered a crash in which he came into contact with a roadside sign and was also forced to abandon the race.
UAE Team Emirates rider Ackermann went on to claim his third career Giro stage win after beating Jonathan Milan (Bahrain Victorious) to the line in a photo finish at the end of the race's longest stage.
"It's a very special victory for me," German rider Ackermann said. "I showed I can do it and I'm super happy today. All the sprinters are very strong and it was a very tense finish."
Welshman Thomas retained the maglia rosa after maintaining his slender two-second lead over Slovenia's Roglic. Portugal's Joao Almeida (UAE Team Emirates) rose to third overall.
"Unfortunately Tao is badly injured," Thomas said. "It's obviously a big loss. He was going very well. He was in a really great position and it's very unfortunate to lose him this way."
Thursday's stage 12 is a 179-kilometre ride from Bra to Rivoli.