No trains will run to or from Crystal Palace on Saturday, August the 24th, 25th or Bank Holiday Monday.
Five sets of switches and crossings and 1,500m of track are to be replaced with brand new equipment.
Network Rail says the work will help reduce train delays and improve journeys.
The work will also impact trains at stations from Streatham Hill to Norwood Junction and Sydenham.
There will also be a reduced Southern service through stations including Peckham Rye, Norwood Junction and West Croydon.
Passengers will be able to use their tickets on the Underground, Overground and Buses though.