Liverpool's new bus station has opened off The Strand, and the road is well-served by nearby James Street railway station.
Waterfront residents also urged motorists to find other routes to drive from one end of the city to the other.
Councillor Peter Millea, executive member for regeneration, said: "There is no denying that The Strand is going to be extremely difficult for motorists over the next year or so.
"But that is the inevitable result of schemes taking place in that area. It is not just a question of roadworks for roadworks' sake..
"All the parties involved are, wherever possible, working together to mini-mise disruption.
"For example, utility companies planning to work at different times have been brought together so we do not have road being dug up a few weeks after another company has finished.
"We would give drivers the assurance that we are doing all we can to ensure traffic can flow smoothly."