A six-storey block of offices and shops will be knocked down to make way for a public square in Cardiff city centre.
The demolition of St David's House will begin this week, with the whole of Scott Road closed for three weeks from Monday.
Work forms part of the wider Central Square development that includes a new BBC Wales headquarters and bus station.
A statue of Wales' first black headteacher Betty Campbell will feature in the square.
She was chosen by the thousands of people who voted in a BBC Wales poll and the monument is set to be unveiled in 2020.
Speaking in 2017, then Cardiff council leader Phil Bale said the square was a major part of the city's regeneration and would help link the Principality Stadium to the Central Square development.
All tenants of St David's House had moved out by January ahead of the demolition.