Police said eight people were taken to hospital, two via air ambulance, but it is believed none had serious injuries.
The tanker was heading south on State Highway 1 when it rolled just north of Mataura about 7.10pm.
The 48-seater bus, carrying 11 passengers from Invercargill to Dunedin, collided with the crashed tanker.
As a result of the impact both tanks ruptured, spilling milk into a highway side ditch.
Ritchies Transport managing director Andrew Ritchie, of Auckland, said it was ''not a very pleasant accident''.
Mathew Grace, who lives near the scene, heard ''a sound like thunder'' when the crash occurred.
He and his wife Lisa, who has first aid training, joined other neighbours in rallying round to help, including by providing blankets.
The milk tanker was carrying milk for the Open Country dairy company and it is understood the firm's milk transport is contracted to Southern Milk Transport.
The state highway was re-opened at 3am.
Police investigators, including members of the Commercial Vehicle Investigation Unit are investigating the incident.
