Some 25,000 people a day are expected to attend the music festival, which features Jake Bugg, Jess Glynne and Mumford & Sons on the Saturday main stage and Coldplay, Ellie Goulding and Years & Years on the Sunday.
Festival goers will be using Exeter Racecourse as a park and ride venue and the Kennford area of the A38 is expected to experience heavy traffic over the weekend.
Gareth Price, Highways England emergency planning officer for the south west, said:
Our aim is to keep the Highways England network running whilst keeping road users safe and informed, and we advise all road users to check our traffic and travel information channels, set off early and allow plenty of time.
Highways England provides live traffic information via its website or from a phone or mobile device.
Travel information is also available by phone from the Highways England Customer Contact Centre on 0300 123 5000 and updates will be provided via Twitter.
Members of the public should contact the Highways England customer contact centre on 0300 123 5000.
Journalists should contact the Highways England press office on 0844 693 1448 and use the menu to speak to the most appropriate press officer.