At least 29 others were wounded when the bomb went off in a busy commercial street during the afternoon rush hour.
It detonated as a car passed carrying a local official, who escaped unhurt. It was not clear if she was the target.
Cotabato is on the island of Mindanao, which has been racked by a 40-year conflict between government forces and Islamist rebels.
It is the second deadly bombing on Mindanao in 10 days. A blast in the city of Cagayan de Oro on July 26 killed eight people.
'Threats'
The local official whose armoured car was hit by Monday's bomb blast, city administrator Cynthia Guiani-Sayadi, had reportedly received threats over the past few days.
Although Ms Sayadi was not hurt, a bodyguard who was in another vehicle was among those killed. Police officers were also among the casualties.
The bomb caused a fire which engulfed nearby cars and commercial premises. The blast was so powerful it was heard "kilometres away", regional governor Mujiv Hataman told the AFP news agency.
Cotabato, which is home to both Muslim and Christian communities, has previously been hit by attacks blamed on Islamist militants and organised criminals.
No group has said it was behind Monday's attack, but correspondents say suspicion is likely to fall on the Bangsamoro Islamic Freedom Fighters (BIFF).
Last month, two soldiers and five guerrillas were killed in an ambush by the BIFF, a breakaway faction from the Moro Islamic Liberation Front (MILF).
The MILF has entered into peace talks with the Filipino government. The decades-long conflict between the state and the MILF has cost an estimated 120,000 lives.
The Philippines has faced separatist movements for decades in Mindanao, where the MILF is based, and in Jolo, home to the radical Islamist Abu Sayyaf group, which is reputedly linked to al-Qaeda.
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