Nursery Street, near the Derek Dooley Way section of the A61 inner ring road, was closed in both directions after the fire ignited in the early hours of the morning.
About 30 firefighters, using five engines and a hydraulic appliance capable of reaching greater heights, were called to the scene at about 6.30am.
This was later reduced to two crews as the blaze came under control.
A spokesman for South Yorkshire Fire and Rescue said the crews arrived to find “a three-storey, 20x40m building, well alight, with fire damage throughout the building.”
South Yorkshire Police tweeted a message to drivers asking them to avoid the area, saying that roads in the area were closed due to “thick smoke” blowing across the area from the fire.
Although Nursery Street reopened at lunchtime yesterday, neighbouring Johnson Street remained closed.
Meanwhile, Bramall Lane was also temporarily closed yesterday morning, during the hour, after a four-year-old girl was hit by a van.
A spokesman for South Yorkshire Police said: “At around 8.40am, police attended a road traffic collision involving a pedestrian and a transit van.
“The collision is believed to have occurred on the crossing near to the football ground on Bramall Lane.
“A four-year-old girl has been conveyed to hospital with a suspected broken leg. At this time, the circumstances of the collision are not known.”