Firefighters tackled a massive blaze at a former Odeon cinema throughout the night and many remained at the scene this morning.
Police, paramedics and 12 fire engines were called to the site adjacent to Evoque nightclub where huge black plumes of smoke billowed across the city.
Two aerial ladder platforms and an air support unit were also in attendance as fire crews attempted to put out the blaze, reported LancsLive.
Police closed off nearby roads in Preston, in the third fire to hit the city centre in days and a number of the roads remain closed today.
This morning, Lancashire Fire & Rescue Services said that the fire was now "under control" but that the firefighting operation continued and eight engines remained at the incident.
Last night fire officials urged people to stay away from the area at the time and warned anyone nearby to keep their windows and doors shut.
Photos and videos taken at the scene showed the building, that is the site of the once popular cinema, had suffered significant damage.
The building on Church Street sits adjacent to another iconic but now empty site where Evoque and Tokyo Jo's was based.
Two "rogue drones" flown around the incident hindered the emergency services battle against the blaze.
In the past week there was also a blaze which took three hours to put out in the city centre last Saturday, and the day before that there was a fire at St Joseph's Orphanage on Mount Street.
Lancashire Fire and Rescue Service said this morning: "Eight fire engines and one aerial ladder platform remain at this incident. The fire has been brought under control however firefighting operations continue.
"Road closures remain in place. This is expected to cause disruption to the city centre this morning, so please avoid the area."
Last night they said: "12 fire engines from Preston, Bamber Bridge, Fulwood, Wesham, Leyland, South Shore, Blackpool, Great Harwood, Hyndburn, Penwortham and Tarleton; two aerial ladders platforms from Preston and Blackpool; the air support unit; and a command support unit from Blackburn are in attendance at a large building fire on Church Street in Preston.
"The building is partly derelict with some parts also used for commercial purposes. Firefighters wearing breathing apparatus are using hose reels and ground monitors to bring the fire under control.
"We are working with Lancashire Police, Preston City Council and other partners in a multi-agency response to the incident.
"Road closures are in place and crews are expected to remain in attendance overnight. Please avoid the area and keep your windows and doors closed if you are affected by smoke."
On the series of fires to hit the city Matthew Brown, leader of Preston City Council, said: "The recent fires taking place in Preston City Centre are very disturbing suggesting a possible trend.
"It has been raised by senior members and officers with both fire and police services. We will continue supporting our emergency services to effectively deal with the matter."
