City Quays 3 has a proposed cost of £46m and will be 16-storeys tall.
With a target completion date of late 2019, it will provide Grade A space for 3,000 staff.
The harbour said it will support 600 jobs during its construction phase.
It will be situated beside a hotel, which is currently being built, and two other office developments.
Graeme Johnston, the harbour's property director, said the move "is a reflection of how strong the demand for quality office space in Belfast is".
He added that at 250,000 sq ft, City Quays 3 will be one of the largest office developments in Northern Ireland.
City Quays 1 is home to, among others, US law firm Baker & McKenzie, while City Quays 2 is nearing completion.
Belfast Harbour has submitted a planning application for what would be a third major waterfront office block.