The Tarka rail line between Barnstaple and Crediton will be closed for two weeks from this weekend.
Passengers will be taken on buses between the towns from Saturday, November 17 until Monday, December 3.
Network Rail will be renewing the track at Lapford and also between Eggesford and Portsmouth Arms.
It says the work will make the train ride smoother for passengers and help pave the way for faster journey times.
Further track renewal improvements are planned between Crediton and Yeoford and in the Umberleigh and Chapelton areas next March.
Network Rail said the programme of improvements brings the total spend on the line to £9.3m to date in the current financial year.
Richard Burningham, manager of the Devon & Cornwall Rail Partnership, said: "These major works are a huge statement of confidence in the Tarka Line and will stand the line in good stead for decades to come.
“It is not so very long ago that people feared the line would close.
“Now we are seeing the biggest investment for more than 100 years.”
“I hope people will check their travel plans before setting off. The two weeks of closure will, of course, inconvenience passengers but I am sure people will appreciate that it is in a very good cause indeed."
John Burch, chairman of the Tarka Rail Association, said "We are delighted that this work is going ahead on the Tarka Line at long last. We have been involved in discussions about these plans for a very long time.
"We have worked hard to raise the profile of the Tarka Line and attract investment to improve the service offered.
"Our ultimate aim is to see faster services on the line and an increase in line capacity to cope with the huge increase in the number of people using the Tarka Line in recent years.
"We realise that suspension of the train service over parts of the line is a huge inconvenience to customers, but this is the best and quickest way to undertake this extensive work.
"We are also working with First Great Western to ensure that suitable replacement road services are operated during the works and believe that short term pain will bring significant long term gain.”
On completion, nearly nine miles of track, just under a quarter of the line's 39 miles, will have been renewed, replacing track which had an average age of 55 years, with some of the earliest components dating back to 1942.