Four nights of cleaning up on the A27 and A23 will begin on Monday 30 January.
Permission for the clearing to begin has been granted by Highways England, who manage the roads, after an application was sent to them by Brighton & Hove City Council.
The work will be carried out by Cityclean staff who will be collecting litter from grass verges and remove any flytipped items.
Cllr Gill Mitchell, Chair of the Environment, Transport & Sustainability Committee, said: “It’s important that we keep our highways clear of rubbish. Not only does litter thrown onto roads create a safety hazard to other vehicles but it’s harmful to the surrounding environment and a threat to wildlife.
“Both the A23 and the A27 are main routes into Brighton & Hove and we should keep them clear to create a good first impression for people visiting the city.
“Keeping Brighton & Hove clean and tidy is hard work but the Cityclean team always do their best and provide great results.”