Fire crews were called to Southampton General Hospital at 5.30am.
Patients have been evacuated and roads surrounding the hospital have been closed by emergency services.
The hospital said the fire is now contained and no injuries have been reported.
The cause of the blaze is not yet known.
The hospital said its emergency department was diverting patients away unless their condition “is deemed life or limb threatening”.
It said visitors are being asked to stay away and all planned outpatient appointments on Sunday are cancelled.
