Southern and Thameslink trains will not call at London Bridge station from Saturday 20 December to 4 January.
From 22-24 December, some Southeastern Charing Cross services will not call at London Bridge in the morning peak.
The disruption results from work to open two new platforms.
Simon Blanchflower, Network Rail's Thameslink programme director, said the closure would result in the new platforms for Southern services from 5 January.
The massive works will bring other changes.
Mr Blanchflower explained: "In the medium term, we'll be opening a new concourse from summer 2016.
"When we have completed all our works here in 2018 there will be a fantastic new facility, a new concourse the size of Wembley football pitch, new retail facilities, new travel opportunities for passengers in terms of the range of destination they can reach from this station."
Transport for London (TfL) has warned that other services on National Rail, London Overground, London Tramlink, DLR and the Tube will be busier than usual as a result of the work.
Source: Network Rail
Works will also take place to modernise nearby track and signalling equipment as part of the Â£6.5 bn Thameslink works programme.
According to Network Rail over 117 million people a year go to London Bridge or through it to Cannon Street and Charing Cross - 54 million start or end their at London Bridge itself.
Platform six is the busiest in Europe serving 18 trains per hour.
Visit BBC London Christmas and New Year travel information for more.
Passengers can expect travel disruption as one of London's busiest transport hubs partly closes over Christmas and New Year, rail authorities have warned.