The accident happened before dawn, and rescue workers were called at 5:05 am.
Eight women and seven men died at the scene near Pretoria, while 37 others were taken to hospital. Seven were in critical condition, emergency services said in a statement.
"Emergency services arrived on scene to find a bus and truck that collided head-on, with multiple patients lying around and some still trapped inside both vehicles," the statement read.
The road was closed throughout the morning. An investigation into the accident's cause has been launched.
South Africa's roads are among the most developed on the continent, but safety remains an issue.
Nearly 1,500 people died on the roads during the last Christmas holidays, which is South Africa's peak summer travel season.