About 90 homes in Railton and surrounds may be hit by floodwaters about lunchtime on Thursday after extensive rain across the northern half of the island state overnight.
The SES has issued an emergency warning for Railton, urging people to enact their flood plans and prepare to leave.
The state's northern half is on high alert for flash flooding, with heavy rain set to continue into Friday morning.
Thursday's 24-hour totals are tipped to reach up to 120mm in the north with isolated totals up to 200mm over higher terrain.
More than 300mm is expected in inland parts of the northwest, which may lead to dangerous and life-threatening flash flooding, particularly in the Western Tiers region.
SES acting director Leon Smith said flood peaks might reach levels seen in the north in mid-2016 when three people were swept to their death.
"It is a very dynamic situation that we're monitoring, but inevitably we will see flooding that will have significant consequences," Mr Smith said.
Swift water rescue teams have been sent to the north in preparation.
Commercial operations at the port of Devonport have been suspended until Sunday due to expected flooding in Mersey River catchments.
The port closure has prompted the cancellation of four Spirit of Tasmania ferry Bass Strait crossings.
Spirit of Tasmania chief executive Bernard Dwyer apologised for any inconvenience and said all passengers would be re-booked on the next available sailing or fully refunded.
He said additional day sailings would be scheduled.
A severe weather warning is in place for half the state, with several rivers subject to flood warnings.
Several evacuation centres have been set up in the northwest and many roads have been closed.
Police Assistant Commissioner Jonathan Higgins urged drivers to be careful, noting many families would be returning from school holidays.
Deputy Premier Michael Ferguson said he was very concerned about the forecast rain and urged people to listen carefully to alerts.
Southwest Tasmania is forecast to receive 30-60mm, with 15-30mm tipped in the southeast, including Hobart.
