According to construction intelligence firm Barbour ABI, Bovis has secured the landmark project, which sits just yards from the British Museum and will see the demolition of the 53m-tall Selkirk House, a former Travelodge hotel, to make way for a 19 storey tower.
Demolition firm John F Hunt will begin clearing the site next week.
The new-build scheme has been brought forward by developers Simten and BC Partners.
Designed by DSDHA, the One Museum Street scheme forms part of a wider mixed-use masterplan at the edge of the Bloomsbury conservation area.
The development will see construction of the main office tower fronting Museum Street, with two six-storey residential buildings on High Holborn and Vine Lane. West Central Street will see a mix of new and refurbished buildings also rising up to six storeys.
The entire project will retain and restore seven heritage buildings to create 44 homes, alongside 180,000 sq ft of new-build office space and ground-floor retail across the site.
The job is expected to sustain over 370 construction jobs annually across the 39-month build programme.
Gardiner & Theobald is acting as project manager and cost consultant. Heyne Tillett Steel is on board as structural engineer, with Scotch Partners appointed for M&E design.