Denbighshire council bought a terrace of properties on Queen Street to make way for new apartments and retail units.
However, structural engineers raised concerns about the condition of some and part of the road was closed to traffic earlier this year.
It will be closed again from Monday as demolition work takes place.
The buildings being demolished are numbers 43 to 47, which was an adult shop, and 49 to 55, which were already derelict and had been knocked through inside a number of years ago.
While the road will remain open to pedestrians and for businesses, the council hopes to reopen it for through-traffic in July.
A main road in Rhyl will be closed to through-traffic from Monday while buildings are demolished.