Volunteers, soldiers and rescue crews used helicopters and boats to evacuate thousands of people stranded on their rooftops in the wake of devastating rains.
Monsoon season starts in June every year but the death toll has soared in the past 24 hours.
Dramatic footage shows homes destroyed by flood waters and houses submerged under the water, as residents use boats and makeshift paddles to rescue their loved ones.
The popular tourist destination has been devastated over the past eight days by heavy rains that triggered flooding, landslides and cause bridges and homes to collapse.
Schools have been shut in the region and air and train services severely disrupted.
Local media reports that the state is now facing a new crisis with some hospitals facing shortages of oxygen and gas stations running short of fuel.
The top state elected official, Pinarayi Vijayan's office tweeted: "Kerala state is facing its worst flood in 100 years."
Rescuers moved quickly during the brief respite from rain to take those marooned by floods to 1,500 state-run camps, using more than a dozen helicopters and about 400 boats.
Vijayan confirmed that at least 324 people had died and more than 220,000 had taken refuge in 1,500 temporary camps.
The New Delhi Television news channel reported that the state was facing a new crisis with some hospitals facing shortages of oxygen and gas stations running short of fuel.
The monsoon flooding has severely hit 12 of Kerala's 14 districts, with thousands of homes damaged since June.
Crops on 32,500 hectares (80,300 acres) of land have also been damaged, the Home Ministry said.
The international airport at Kochi, a major port city, suspended flight operations until Saturday after the runway was flooded. Authorities also asked tourists to stay away from the popular hill station of Munnar in Idukki district because of flooding.
More than 1,000 people have lost their lives in seven states since the start of the monsoon season in June.
A total of 407 people have died in Kerala, 190 in Uttar Pradesh, 183 people in West Bengal, 139 in Maharashtra, 52 in Gujarat, 45 in Assam and 11 in Nagaland state, officials and the Press Trust of India news agency reported.
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