The accident took place at around 4:30 a.m. on the Saigon Bridge as the man drove from District 2 to Binh Thanh District in Ho Chi Minh City, police said.
He drove straight on into a refrigerated truck driven by 50-year-old Luu Quang Tai. The crash killed the South African on the spot and destroyed the motorbike.
It took police until 9 a.m. to clear the scene and for normal traffic to resume on the bridge.
Local authorities, who did not release the identity of the dead man, said they were investigating the accident.
According to the National Traffic Safety Commitee, Vietnam recorded more than 5,500 traffic accidents that killed 2,667 and injured 3,965 people in the first five months this year.
The committee said in most cases, the main reason for the accidents was violation of lane rules.