Images of smoke billowing from the area, believed to be a scrap metal recycling business, have been shared on social media.
One picture shows smoke from the harbour, as seen from over 6 miles away in Jordanstown.
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Emergency services including the Northern Ireland Fire and Rescue Service are at the scene.
Four fire appliances are assisting in tackling the blaze, alongside two specialist vehicles and two specialist officers.
A PSNI spokesperson said: 'Police are currently in attendance as Northern Ireland Fire & Rescue Service are dealing with a fire at waste ground in the Queen's Road area of Belfast Harbour Estate.
'Motorists are advised to avoid the area and anyone living nearby is asked to keep their windows closed.'