Five hundred competitors - including the 2009 Formula 1 World Champion - and up to 10,000 spectators are expected to travel to the event, which will take place at Markeaton Park.
The slip roads from the A38 to Kedleston Road will be closed from 8.45am to 4.00pm while Kedleston Road is used for the cycle discipline of the event.
Highways England will use signs on approaching roads to give drivers information about likely delays and congestion along this route.
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.