Twelve police officers were killed while 17 others were injured in the blast in Tunis, according to a statement issued by the presidency.
The area in which the incident occured is a known meeting spot for police officers.
No group has yet claimed responsibility for the attack.
The authorities have declared a 30-day state of emergency countrywide as well as a curfew in the capital and in three other provinces.
President Mohamed Beji Caid Essebsi is soon expected to address the nation regarding the incident.
It was the third major attack in Tunisia this year, after a militant killed 38 foreigners at a beach hotel in the resort of Sousse in June, and gunmen killed 21 tourists at the Bardo Museum in Tunis in March. Islamic State claimed both those attacks.
“They want to make us live with horror but we are going to bring that horror to the terrorist camps,” President Beji Caid Essebsi said in a televised speech. “We are at war and we are going to win.”
Security sources said the guards were boarding the bus to be taken to the presidential palace on the outskirts of the city when it blew up. One presidential source said it was likely that a bomber had detonated his explosive belt inside the bus.