Traffic is building both northbound and southbound near the Langstone Bridge area of Langstone Road.
Emergency services are attending the incident, which happened at about 11.30am outside the Texaco Garage south of the bridge, close to the junction with Northney Road.
Police said a Smart car and a Peugeot were involved.
A South Central Ambulance Service spokesman said an elderly woman was in one car and a 26-year-old female and two-year-old boy in the other.
He added: ‘We currently have a paramedic team leader in a rapid response vehicle and two ambulances at the scene assessing all the patients.
‘A third ambulance has been requested which would indicate all three patients will be going to hospital though no-one has left the scene yet.’
Firefighters helped free one of the drivers who was trapped in their car.
Stagecoach South tweeted: ‘Serious RTC just south of #Langstone Bridge. Road currently blocked. #Ser30/31 currently at a stand still.’
Drivers are queuing as far as south as the Stoke Fruit Farm shop, along the Havant Road and as far north as the A27 roundabout.