Officials are expecting the numbers to rise as Lebanese rescue workers continue to dig through the rubble looking for survivors.
The blast happened at a Beirut port warehouse that stored highly explosive material.
It was one of the most powerful explosions in years in Beirut, Lebanon further bringing the country to its knees as it struggles with an economic crisis and a surge in coronavirus infections.
President Michel Aoun said that 2,750 tonnes of ammonium nitrate, used in fertilisers and bombs, had been stored for six years at the port without safety measures, and he said that was "unacceptable".
He called for an emergency cabinet meeting on Wednesday.
Officials did not say what caused the blaze that set off the blast. A security source and media said it was started by welding work being carried out on a hole in the warehouse.
"It's like a war zone. I'm speechless," Beirut's mayor, Jamal Itani, told Reuters while inspecting damage on Wednesday that he estimated would cost billions of dollars.
"This is a catastrophe for Beirut and Lebanon."
The head of Lebanon's Red Cross, George Kettani, said at least 100 people had been killed.
"We are still sweeping the area. There could still be victims. I hope not," he said.
Kettani earlier told broadcaster LBCI that the Red Cross was coordinating with the health ministry to set up morgues because hospitals were overwhelmed.
Hours after the blast, which went off shortly after 6pm (1500 GMT), a fire blazed in the port district, casting an orange glow across the night sky as helicopters hovered and ambulance sirens sounded across the capital.
The blast was heard throughout Cyprus, which is about 100 miles (160 km) away.