The accident occurred near Dinguiraye in Kaolack region, and it came after the government recently unveiled reforms to try and crack down on dire road safety.
"There were 10 dead recorded at the site of the accident, one victim lost their life while being transferred to hospital, and another at the hospital itself," doctor Saliou Tall of the El Hadj Ibrahima Niass Hospital told the official APS news agency.
The west African nation is filled with vehicles in poor condition and a lack of training for drivers is common.
The driver of the bus fell asleep at the wheel the agency reported, citing witnesses.
Local firefighters gave the number of injured as 48, 10 of whom were in a serious condition.
Senegal plans mandatory driving lessons, point-based penalties and more stringent testing of old vehicles, especially taxis, that use its roads.
Senegal's director of road transport said in January more than 600 people died in road traffic accidents in 2016, while two million citizens possess fake driving licences.