Authorities say 287 killed and 167 others missing after heavy rains caused rivers to burst their banks in South Kivu province.
A further 205 people were seriously injured in the flooding caused when rivers burst their banks following heavy rains on Thursday, while 167 people are listed as missing.
President Felix Tshisekedi has declared a day of national mourning on Monday and a team of ministers is set to travel to the region to coordinate humanitarian aid and disaster management, government spokesman Patrick Muyaya said.
The current rainy season, typical for the South Kivu region, is expected to last until the end of May.
The disaster in Eastern DR Congo came two days after floods killed at least 131 people and destroyed thousands of homes in neighbouring Rwanda, which lies on the other side of Lake Kivu.
On Saturday, UN Secretary-General Antonio Guterres offered his condolences to the victims of the “catastrophic floods” in both countries.
“This is yet another illustration of accelerating climate change and its disastrous impact on countries that have done nothing to contribute to global warming,” he said during a visit to Burundi.
Experts say extreme weather events are happening with increased frequency and intensity due to climate change.
Last month, a landslide provoked by torrential downpours killed around 20 people in North Kivu, a province that neighbours South Kivu.
DR Congo, a vast nation the size of continental western Europe, is one of the poorest countries in the world, riddled by conflict in its east.