Bitterne Road will be closed westbound at its junction with West End Road for eight weeks while traffic signals are upgraded.
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The works at the junctions with Peartree Avenue, Angel Crescent and West End Road are due to start on Monday (Sept 28), according to council contractor Balfour Beatty.
Eastbound traffic on Bitterne Road will only be able to turn left into West End Road, with temporary traffic lights used to manage traffic.
There will also be temporary overnight closures of Peartree Avenue and West End Road between Brownlow Avenue and Maybray King Way during the first two weeks, with a diversion in place.
The scheme includes replacing traffic signal equipment and improving pedestrian connections, as well as technology intended to help buses move through the junction.