Chiltern Railways is to start work to link the line to the London Marylebone mainline, due to open in summer 2015.
The company said it would be the "first new rail link between two major British cities for 100 years".
Replacement buses are in place from Saturday with ticket prices remaining the same and with room for bicycles.
The last services will be the 23:12 Oxford to Bicester Town and the 23:42 Bicester Town to Oxford.
Bicester Town station is being rebuilt and a new station called Oxford Parkway will be constructed to serve the north and east of the city.
The line between Oxford Parkway and London Marylebone will open in summer 2015.
The full line between Oxford and London Marylebone is expected to open in spring 2016 once upgrades to Oxford railway station are completed.
Approval for the Â£130m route was granted in May after the High Court turned down a bid to block it on environmental grounds.
The Oxford to Bicester Rail Action Group (OBRAG) had concerns about having enough buses during peak hours while work is carried out.
Chairman Ian East said commuters "face a significantly longer journey time by bus, with the prospect of getting stuck in traffic jams".
But Chiltern Railways business development director Graham Cross said the firm had worked hard to meet passenger demand.
On completion the train journey times between Oxford and London Marylebone are expected to be 66 minutes.
Train services on the Bicester to Oxford line are stopping for two years so work can start on a high speed line to London.