Fatbergs are caused when cooking fat, oil and grease are poured down drains and become tangled up with waste items like baby wipes and sanitary products.
The blockage is in a sewer beneath the Dublin Road in Belfast.
Northern Ireland Water said crews have already removed "a couple of hundred tonnes" of grease from the sewer.
The firm said cooking fat is a "significant" problem in the area as it houses several fast food outlets.
The company's networks sewerage manager, Gavin McCready, warned restaurant owners that fatbergs could have some very unpleasant side-effects.
"These fat blockages can not only result in out-of-sewer flooding, but odour problems and the risk of rat infestations both near and beyond your premises."
Mr McCready also said it was adding unnecessary costs to the businesses and the public purse.
"While most businesses use grease traps and bin their waste correctly, those that don't are contributing to a massive fatberg in the sewers around the area.
"Our team has been on the site, working over a number of Sunday mornings, clearing the fat that has solidified.
"This is labour intensive work that can only be done early in the morning before the traffic builds up."
In the last two years NI Water has spent over Â£5m clearing blockages from the sewer system.
The company said up to 80% of blockages were caused by fat, oil and grease and other inappropriate items being flushed into drains.
The items get stuck together and form a ball, which can build up over time to block sewer pipes.
Earlier this month, NI Water spent five hours clearing a fatberg from a drain in Newry, County Down.
The blockage was at Buttercrane Quay in the city centre.
In August 2013, Britain's biggest ever fatberg was removed from a London sewer.
Thames Water said the lump found under a street in Kingston upon Thames was the size of a bus.
An operation to remove a "massive fatberg" from a Belfast sewer has been ongoing for the last six Sundays and is expected to take several more.