The B4386 between Shrewsbury and Yockleton has been shut as a result of the incident, which has seen three other people also taken to hospital.
Station manager Jim Barker asked people to avoid the area while they deal with the crash, which was in the area of Cruckton.
Two fire crews were sent to the scene after they were alerted at around 11.20am.
West Midlands Ambulance Service said four people had been taken to Royal Shrewsbury Hospital after the crash after they had been called to attend at 11.11am.
A spokesman said: "Three ambulances and a paramedic officer attended. Crews arrived to find a collision involving a three car RTC with all occupants out of the vehicles.
"One man, the driver of a vehicle, suffered potentially serious injuries and was given treatment on scene before he was conveyed on blue lights to Royal Shrewsbury Hospital.
"A second man, a passenger from another vehicle, suffered injuries and was taken to the same hospital. The driver and a passenger from the same vehicle were assessed on scene and were also taken to the same hospital for further checks."