It will affect CrossCountry and Great Western Railway (GWR) trains travelling between Didcot, Oxford and Banbury.
Chiltern Railways services from Oxford use a different line and will not be impacted by the project which is designed to enable trains through Oxford to reach higher speeds.
James Davis from GWR said it was the operator's "quietest period".
Chiltern Railways will be adding extra carriages at peak times but has warned passengers its trains may be "busier than usual".
Replacement bus services will be brought in on some services.
Network Rail said it had worked with the rail operators to minimise the impact on passengers during the project, which ends on 30 July.
Engineering work which will disrupt rail services through Oxfordshire for nine days starts this weekend.