The westbound side on Brighton seafront will be reopened between roughly 8.30pm and 9.30pm, according to a highway officer.
It has been closed for almost three weeks since the devastating Royal Albion Hotel fire on July 15.
The A259 will close again on Saturday due to the Pride parade which goes along King’s Road, West Street and down North Street in Brighton.
The eastbound side of the A259 will remain closed for “several weeks” according to Brighton and Hove City Council.
Council leader Bella Sankey said: “I want to thank people for their patience while we work hard to make the Royal Albion Hotel site safe and secure.
“I know this terrible fire at the hotel has affected many people, from neighbouring residents to local businesses and those travelling around our city.
“I’m pleased that we’re able to reopen the westbound carriageway of the A259 this week, which will help ease congestion in the city.”