Flooded homes along the River Thames are being evacuated and thousands more are at risk, with water levels expected to keep rising for the next 24 hours.
Residents in one Berkshire village say the scenes are from a "horror movie".
Fourteen severe flood warnings are in place in Berkshire and Surrey, while two remain in Somerset.
PM David Cameron, who is touring flood-hit south-west England, said it was not the time to change personnel amid criticism of the Environment Agency.
Chancellor George Osborne, meanwhile, said people understood "that the rain is not the fault of any one person".
Homes, shops and businesses in the Berkshire village of Datchet are underwater and hundreds more along the lower River Thames, as far as Shepperton, are under threat, the Environment Agency says.
Several Thames gauges are showing their highest levels since being installed in the 1980s and 90s.
Fire crews, who have been rescuing people from their homes in Staines-upon-Thames, say they have never known waters so deep or a flood rescue operation on this scale.
On Monday night, Surrey Police said more than 150 people had been rescued from flooded homes in the previous 24 hours.
In Windsor, Councillor Colin Rayner pleaded for help from the police and Army.
"We've got 50 volunteers here, we've got the vulnerable people out of their homes, now we need to get everyone else out," he said
Nearby, in the Berkshire village of Colnbrook, resident Asif Khan said his whole street was under water, his house was flooded and his fridge "just went bang".
"It's something out of a horror movie," he said, adding that he was now about to try to evacuate with his two small children.
Hurst village resident Paul Palmer said sewers there were blocked and they have been unable to use the toilet since Friday.
"It's starting to back up into the toilet - it's like going back to the dark ages," he told the BBC.
Thames Valley Police have declared a "major incident" in east Berkshire.
A major incident has also been declared in Surrey by the county's police force.
Howard Davidson, from the Environment Agency, said he expected conditions in the county to deteriorate as more rain fell over the coming days.
"We have issued flood warnings from Datchet down to Shepperton, and we urge people to take heed of the flood warnings. We are anticipating another three or four inches on the Thames over the next 24 hours."
The Environment Agency said it had never issued as many severe flood warnings and that many areas had seen more than double their average rainfall.
A two-hour meeting of the emergency Cobra committee has taken place.
The prime minister took part by phone from south-west England, where he will spend the night.
Speaking afterwards, Communities Secretary Eric Pickles said sites likely to have problems in coming days were being identified and prioritised.
"Everything possible" was being done to protect homes and communities, and special attention was being paid to water and electrical plants, he added.
The control of sandbags and ordering of temporary flood defences would be centralised by government, he said, and "full military support" remained on standby across the south.
Railway lines have also been badly affected with passengers facing severe delays. The latest developments include:
- Trains between Staines and Windsor and Eton have been cancelled until at least Thursday
- First Great Western says mainline services from London Paddington had resumed but a reduced timetable was running between Paddington and Reading
- The main route into and out of Devon and Cornwall, via Bridgwater, has been cut off by floods and storm damage
- First Great Western has lifted ticket restrictions on all journeys
Among other developments:
- The Environment Agency has issued 14 severe warnings - meaning "danger to life" - along the River Thames, in areas including Staines, Chertsey and Datchet
- Two severe warnings are in place for the South West of England in Salt Moor and East Lyng, in Somerset
- Large parts of Worcester city centre could be closed for a week because of flooding, the county council has said.
- An earth bank has been built to protect the town of Bridgwater, on the edge of the Somerset Levels, from flooding
- The family of Gareth Lockyer, the missing a kayaker whose body was found in the River Usk in Powys, say he was a "kind, caring and gentle" person
- Essex County Council says it is releasing £1m of emergency funds to tackle road flooding across the county
Network Rail says it is concerned about 400 to 500 railway sites. Normally, at this time of year, it would be about a dozen.
It is also warning that problems on the rail network could last for some months.
More than 300 less serious warnings and alerts have been issued by the Environment Agency, mostly in southern England and the Midlands.
BBC Weather forecaster Steve Cleaton said rain and strong winds were expected to hit areas already affected by flooding on Tuesday.
It is expected to start raining on the Somerset Levels at between 2am and 3am, with 10-20mm falling widely and as much as 30mm in some areas.
The band of rain is due to approach the Severn basin by dawn on Tuesday and the Thames areas around the time of the morning rush hour.
Wednesday will bring wintery showers, gale force winds and heavy rain in parts of south and west England, Mr Cleaton said, with gusts of over 70mph expected in Devon and Cornwall.
Minister Eric Pickles answered an urgent question put by Labour in the Commons on the flooding crisis.
Mr Pickles, who is standing in for Environment Secretary Owen Paterson, told MPs that there was a "high risk that the Thames, the Severn and the Wye will flood in the middle of the week".
But he said extra efforts were being made to deal with the problem.
He also denied making "even the slightest criticism of the work of the Environment Agency", amid a row over his suggestion last week that ministers had been given bad advice by the agency over river dredging.
Speaking from Portland, off the Dorset coast, Mr Cameron said: "I am only interested in one thing and that is making sure that everything government can do is being done and will go on being done to help people through this difficult time."
Chancellor George Osborne told ITV's The Agenda: "We're investing in the frontline services now to get these rail lines repaired, to protect homes along the Thames at the moment, the homes in Somerset, bring in the Army and all that kind of thing.
"It does lead to a real debate about how we look after our countryside."