Emily Whitaker from organisers Motiv Sports said the new start location would remove a city centre loop early in the race.
She said: “It improves the runner experience by getting out of the city a bit sooner in the race and on to some of the wider roads.
“Also it just generally will reduce congestion around the city centre, we hope.”
The 13.1-mile (21km) course weaves past some of the city’s iconic architecture, as well as the River Cherwell and Old Marston village.
The finish line has been moved from Parks Road to Mansfield Road.
Part of Mansfield Road and Savile Road will be shut from 12:00 on Saturday to prepare the start and finish areas.
On Sunday, part of Parks Road, Holywell Street and Jowett Walk will be closed from 05:00.
Runners are urged to arrive at the event village in Oxford University Parks by 08:30, ready for the start at 09:30.
Organisers said park and ride sites would be busy. They have added a new race-specific park and ride facility at Unipart House.
Most roads will be reopened as runners pass, with last finisher expected at 13:45, they added.
