The £20m contract is with wind farm developer Scottishpower Renewables.
The engineering firm is to make 24 steel foundation jackets for wind turbines to be used in the North Sea. The work will take two years to complete.
Harland and Wolff said the new contract is "very significant for Belfast".
It added that the structures, at more than 65m tall, will almost be as "prominent in the Belfast skyline as the famous Samson and Goliath cranes".
Harland and Wolff stopped shipbuilding in 2003 and its more recent work has included refurbishing oil rigs.
In March, it announced 60 jobs were to go because of a downturn in the offshore oil and gas sector.
Accounts for last year show it had made a profit of £1m and described market conditions as difficult.
Harland and Wolff has secured a major manufacturing contract that it says will support 200 jobs.