Sixty firefighters responded to 30 flood-related calls which were made at around 6 pm.
Several roads closed due to heavy rain have since reopened but motorists have been advised to remain cautious.
The Fire & Rescue Service confirmed two specialist water teams and six appliances were involved in the rescue effort.
Speaking on Radio Ulster’s Good Morning Ulster programme, NIFRS group commander Keith Black said they called to 80 properties in Sion Mills.
He said there were eight to 10 inches of water places with some deeper localised patches.
Mr Black added that there would be a multi-agency effort to assist residents affected by the flooding although there was not yet any indication of the damage caused.
Areas affected in Sion Mills included Garden Terrace, Parkside Gardens and Melmount Road.
Deputy Mayor of Derry City and Strabane District Council SDLP councillor Cara Hunter, who said it was the worst flooding for years, added: “This is an ongoing problem.
“In Sion Mills we are seeing two, three feet of water and it is now entering homes.”
Sinn Féin MP Órfhlaith Begley said more than 30 homes had been flooded.
She said buses had been put on to take those affected from the village.
“This flooding has been extremely distressing for local residents and every effort must be made to support them and to ensure it does not happen again,” she added.
Melvin Hall Community Centre was opened for anyone who had to leave their home and an incident centre was set up at McGillion’s garage in the village.