Hundreds more were wounded when a lorry packed with explosives detonated near the entrance of a hotel.
It is the deadliest terror attack in Somalia since the Islamist al-Shabab group launched its insurgency in 2007.
President Mohamed Abdullahi "Farmajo" Mohamed blamed the attack on them, calling it a "heinous act".
No group has yet said it was behind the bombing.
"Brothers, this cruel act was targeted at civilians who were going about their business," the president said.
He has declared three days of mourning for the victims of the blast.
Local media reported families gathering in the area on Sunday morning, looking for missing loved ones amid the ruins of one of the largest bombs ever to strike the city.
Police official Ibrahim Mohamed told AFP news agency the death toll was likely to rise. "There are more than 300 wounded, some of them seriously," he said.
Officials also confirmed that two people were killed in a second bomb attack in the Madina district of the city.
Mogadishu's Mayor Thabit Abdi called for unity while addressing a crowd of people who had gathered to protest.
"Oh, people of Mogadishu, Mogadishu shouldn't be a graveyard for burnt dead bodies," he said.
"Mogadishu is a place of respect, and if we remain united like we are today, moving ahead, we will surely defeat the enemy, Allah willing."
A BBC Somali reporter at the scene of the main blast said the Safari Hotel had collapsed, with people trapped under the rubble.
An eyewitness, local resident Muhidin Ali, told AFP it was "the biggest blast I have ever witnessed, it destroyed the whole area".
Meanwhile, the director of the Madina Hospital, Mohamed Yusuf Hassan, said he was shocked by the scale of the attack.
"Seventy-two wounded people were admitted to the hospital and 25 of them are in very serious condition. Others lost their hands and legs at the scene.
"What happened yesterday was incredible, I have never seen such a thing before, and countless people lost their lives. Corpses were burned beyond recognition."
The international community has been quick to condemn the attack:
- African Union Commission's president Moussa Faki Mahamat said the body would continue supporting Somalia in efforts "to achieve sustainable peace and security"
- Turkey said it would send planes with medical supplies, and fly wounded people to Turkey for treatment
- In a statement, the US Mission to Somalia called it "cowardly" and said it reinvigorated US commitments to help African countries fight terrorism
- UK Foreign Secretary Boris Johnson said his thoughts were with victims' families and the government and people of Somalia. "Those responsible have shown no regard for human life or the suffering of the Somali people," he continued
- UN Secretary General Antonio Guterres tweeted that he was "sickened" by the attacks and urged "unity in the face of terrorism and violent extremism"
- French President Emmanuel Macron tweeted that France stands by Somalia's side
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