River Nyamwamba has burst its cutting off Kasese-Fort Portal in Kasese district.
The incident happened at Wednesday night at 2am which saw residents flocking Kasese town for safety.
Some say they heard sounds of rolling stones on the slopes of Mountain Rwenzori being carried down by the bursting rivers.
The floods hit Nyamwamba in Kasese town, Mubuku in Ibanda-Kyanya town council and Nyamughasana in Kyalhumba Sub County.
The Mayor Kasese municipality, Godfrey Baluku Kabbyanga, told Daily Monitor the river overflew at Bunyandiko in Kilembe sub county flooding in the low land areas of the town.
Kyanzuki Bridge on River Nyamwamba has also been swept away.
Several people have now fled their homes and are now encamped at Ibanda Primary School.
River Kithakena in Maliba Sub County has also overflown causing flooding in the neighbouring areas of Kachindo and Maliba Trading Center.
The extent of the damage is not yet known.