It has already affected five units on Broughshane Street and the fire service are currently trying to stop the fire from spreading further.
One firefighter has been slightly injured while tackling the blaze which began at 17:00 BST at the Woodgreen furniture store.
Police have said that Brougshane Street will stay closed overnight on Tuesday.
Traffic is being diverted at Chapel Roundabout.
Motorists are being asked to avoid the Broughshane Street, William Street and Broadway Avenue areas of the town.
Eyewitness Emma Hamilton had been shopping in Broughshane Street just minutes before the fire was spotted.
She filmed the flames from a car park on the roof of a nearby shopping centre.
"We could see a large plume of black smoke and straight away ran over to see what it was", she told BBC Radio Ulster.
"We could see, over into Broughshane Street, two buildings heavily ablaze, with the roofs of the adjoining properties on either side starting to disintegrate, and flames coming through those as well."
Houston Bell, who works in Ballymena, was driving home when he spotted the blaze and stopped his car to film the incident on his mobile phone.
He told BBC News NI that several shoppers walked past the shop just as the fire was taking hold, unaware of the flames above them.
Mr Bell said warnings were shouted at people on the street to get back from the shop front, and he described hearing the sound of breaking glass as he drove away from the scene.
An estate agents, whose premises was damaged in the blaze, has said that all its diaries and contact details for clients have been destroyed.
Writing on Facebook, Rainey & Gregg thanked "everyone for their kind words and offers of help".
Group Commander Brian Stanfield said there were five fire engines and two aerial appliances at the scene.
A "significant" fire has broken out at a furniture shop in Ballymena, County Antrim and spread to adjoining shops.