There will be no trains from Northampton to London Euston this weekend.
All train lines to and from London Euston will be shut on September 1 and 2 while the final stages of work to replace North Wembley Junction are carried out.
West Coast main line customers are being urged not to travel to and from London this weekend.
The rail company says if customers absolutely cannot avoid train travel, they can expect busier trains, longer, diverted routes and train timetable changes.
Martin Frobisher, route managing director for Network Rail’s London North Western route said:“Our message to West Coast train customers this weekend is: ‘Do not travel.’ Instead please plan your journeys on other days.
“If you absolutely cannot avoid travel on these dates, expect a very different journey to what you’re used to – busier trains, less chance of a seat, diverted routes taking far longer than usual.
“There is never an ideal time to shut the railway but these weekends have been the least disruptive times to do it.
“We have worked together for the past three years with train operators to carefully plan this closure of the railway in a way that minimises impact on customers.
“It’s vital the track at north Wembley is replaced to continue to safely meet the huge demand of passenger and freight rail services on the West Coast main line. This work will result in better, more reliable journeys in future.”