The A270 Lewes Road was closed earlier and Dewe Road in the Moulsecoomb area remains closed due to the operation, police say.
The force wrote on social media at 2pm, “Following a report of a suspicious package, Dewe Road, the A270 (Lewes Road) and surrounding roads are currently closed.
“A 100m cordon in place for safety. Affected homes and buildings are being evacuated as precaution.”
People are asked to avoid the area and find alternative travel routes.
A later announcement from police at 3pm confirmed Lewes Road had been reopened.
Ordnance disposal teams have been called to the scene in Dewe Road.
A building at the University of Brighton’s campus in Mouslecoomb is among those which have been evacuated.
The university said in a statement, “We are following police advice and as a precaution, the adjacent Mithras House building has been evacuated. The rest of Moulsecoomb campus is open as normal.”
The latest information from police at 3.20pm said, “We have reopened the A270 Lewes Road, Brighton in both directions.
“The closure of Dewe Road and the surrounding cordon remains in place as we investigate a report of a suspicious package.
“Affected homes and buildings are being evacuated as a precaution.”