The fire began at around 4 p.m. Monday at ADM Milling on the 200 block of Ganson street.
The 10th floor of the flour milling facility caught fire after a piece of machinery malfunctioned.
There were employees inside at the time. All evacuated safely.
More than half of the city's fire force responded because of the challenging nature of fighting a fire in a high rise.
"It's a very labor intensive operation. We have to get water up there. It takes a lot of guys, a lot of persons to do that," said Commissioner Garnell Whitfield, Buffalo Fire Department. "We want to keep them fresh, we want to keep them safe so we are rotating them periodically to make sure they are ok."
The fire is now contained but Whitfield says there is a possibility of dust explosions.