The Runnymede-on-Thames conference hotel in Surrey was forced to close indefinitely on Tuesday (7 January) after the River Thames burst its banks.
The hotel's car park has been flooded and the A308 Windsor Road, which the hotel is located by, has been blocked off by water.
More than 100 guests have been relocated and a number of meetings and events have also been cancelled or relocated to sister hotel The Grove and nearby hotels.
The hotel will remain closed on Thursday 9 January and is likely to open on Friday at the earliest.
More rain is expected to fall and a number of flood warnings are in place for Surrey along the River Thames.
A statement released by the hotel said: "Water levels started to rise significantly in [the hotel's] car parks on the morning of Tuesday 7 January and the senior management team acted promptly to out book hotel, conference and restaurant guests to its sister property The Grove and other local hotels.
"The hotel will be closed until current water levels reduce and will reopen as soon as access via the A308 Windsor Road is restored and its car parks have drained to allow for guest parking.
"The hotel would like to thank all of its customers for their cooperation and understanding and look forward to welcoming guests again soon."
Flooding has also occurred in Staines, Sunbury, Walton and other areas, causing roads and car parks to be closed.
The four-star Runnymede-on-Thames is a major conference hotel with 13 meetings rooms that can host up to 200 people.