The bombs killed at least 81 people, witnesses and officials said, in an attack that bore the hallmarks of Islamist Boko Haram militants.
Blasts from the coordinated assault rang out as scores of people packed into the ancient building's courtyard for afternoon prayers. "These people have bombed the mosque. I am face to face with people screaming," said local reporter Chijjani Usman.
The mosque is next to the palace of the emir of Kano, the second highest Islamic authority in Africa's most populous country and a vocal critic of Boko Haram. The emir, former central bank governor Lamido Sanusi, was not present.
Boko Haram, a Sunni jihadist movement which is fighting to revive a medieval Islamic caliphate in northern Nigeria, regards the traditional Islamic religious authorities in Nigeria with disdain.
(READ MORE: Nigeria needs to attack terrorism)
It has attacked mosques that do not follow its radical ideology in a bloody near six-year campaign that has also targeted churches, schools, police stations, military bases and government buildings.
"After multiple explosions, they also opened fire. I cannot tell you the casualties because we all ran away," a member of staff at the palace told Reuters on Friday.
After the attacks, angry youths blocked the mosque's gates to police, who had to force their way in with tear gas.
Reuters visited two mortuaries, one with 20 bodies from the attack, the other with 61, according to medical officer Muhammad Ali. The victims had blast and gunshot wounds, he said.
President Goodluck Jonathan said in statement that he would "not to leave any stone unturned until all agents of terror undermining the right of every citizen to life and dignity are tracked down and brought to justice."
A MILLION DISPLACED
The old mosque and palace date back centuries to when Kano was one of several Islamic empires thriving off trade in gold, ivory and spices from caravan routes connecting Africa's interior with its Mediterranean coast -- glory days of Saharan Islam that Boko Haram says it wants to recreate.
Islamic leaders sometimes shy away from direct criticism of Boko Haram for fear of reprisals, but Kano's emir Sanusi, angered by atrocities such as the kidnapping of 200 schoolgirls from the village of Chibok in April, has become an increasingly vocal Boko Haram critic.
He was quoted in the local press as calling on Nigerians this month to defend themselves against Boko Haram. During a broadcast recitation of the Koran he was reported to have said:
"These people, when they attack towns, they kill boys and enslave girls. People must stand resolute ... They should acquire what they can to defend themselves. People must not wait for soldiers to protect them."
(READ MORE: A slower Nigerian economy can expect more terror attacks)
The insurgency has forced more than one million people to flee during its campaign focused on Nigeria's northeast, the Red Cross told reporters on Friday, an increase on a September U.N. refugee agency estimate of 700,000.
Persistent insecurity is dogging President Jonathan's campaign for re-election to a second term in February 2015. He has asked parliament for approval to extend an 18-month-old state of emergency in the northeast.