A historic inn overlooking the River Derwent that may have been visited by a young Charles Darwin is about to change hands for the first time in half a century.

The Black Snake Inn, built in the 1860s, epitomises the Tasmanian gothic aesthetic that has become such a drawcard for filmmakers.

It's halfway between New Norfolk in the Derwent Valley and Hobart, and the original property was one of Australia's first ferry inns, providing sustenance and shelter to those making the trip across the River Derwent.

The current house, built in the Victorian Rustic Gothic style, comes with four bedrooms and one bathroom, about 1.4 hectares of land, a standard red brick veneer house and views over the river.

Historian Stefan Petrow from the University of Tasmania said there had been many versions of the inn, from a modest building in the early 1800s to a more significant structure in the 1830s, which burned down and was replaced with the current house.

Over the years it's had a few celebrity visitors.

"There are some reports a young and homesick Charles Darwin started looking around the area and noticed there were some really nice rocks," Professor Petrow said.

"That's some of the descriptions of the area, it was very stony and rocky, so Charles Darwin stopped and looked at the rocks. Whether he went inside and had anything to eat or drink, you can't confirm one way or the other."

Other reported visitors include the Reverend Robert Knopwood — whose diary documents the hard-drinking brutality of colonial life in Tasmania — and Irish nationalist John Mitchel, who was transported to the state to stifle his political ambitions but escaped on a sailing ship in 1853.

The inn hasn't been licensed for around a century and in recent times has been a shop and a private residence.

Owner George Burrows is a collector of antique huon pine furniture and, in 2006, sold an extensive collection to the Tasmanian Museum and Art Gallery with the help of a $740,000 donation from gambling millionaire and MONA owner David Walsh.

It's the first time the Black Snake Inn has been on the open market for 80 years and it is expected to fetch around $3.5 million.

As with all historic home purchases, it comes with baggage.

Agent John Soundy said parts were in "original condition" — meaning they need a lot of work — and a section of the land is likely to be acquired by the government for roadworks leading up to the new Bridgewater Bridge.

A State Growth department spokesperson said in a statement decisions on specific acquisitions would not be made until the design had been finalised and there was a preference for "minimal impacts" on landowners.

Other sections may be approved for subdivision, providing some sort of cash return, but there's no guarantee about the structural integrity of the house itself.

"We'd make no comment about that," Mr Soundy said.

Despite all the hurdles, the agent said he had a stack of expressions of interest "several centimetres high".

"I've had interest from people running distilleries and things like that, and it looks like the new highway going to New Norfolk will run right past the front door, which it doesn't now," he said.

"There are difficulties with what you can do with regards to heritage and the new bridge works, but it's all doable if people are in the frame of mind for reasonable negotiation."