Hoddle Street will reopen to traffic on Sunday night after an eight-day construction blitz.
The arterial - one of Melbourne's busiest - was fully closed to traffic between Noone Street and Victoria Parade since January 7.
Commuters will return to the road for the Monday peak, despite some ongoing lane closures that will be in place until late April.
Right turns are still banned from Hoddle Street into Johnson and Truro streets.
The works marked the start of the Streamlining Hoddle Street Project - a bid to reduce delays on Punt Road and Hoddle Street by changing the way right turns are made, including creating a dedicated right-turning lane onto Olympic Boulevard for people travelling south on Punt Road.
While jackhammers rattled and buses still roared along Hoddle Street, residents have appreciated the break from motorists.
Nuray Benek, who lives in nearby Perry Street, told The Age last week she'd been wandering out to the road at peak hour and standing there - just because she could.
"No traffic. Hoddle Street – it's always noisy, and too much cars, always a busy road," Ms Benek said.
"Too much dust, and noise. The quiet is better for walking. Now I'm feeling the fresh air. I just feel better."