Seven fire engines and at least 40 firefighters were called to a fire at the Thirsty Bear pub in Stamford Street on Wednesday.
Part of the first floor and the extraction system from the first floor to the roof of the building was alight.
Station Commander David Bracewell, who was at the scene, said: "The road is closed between Blackfriars Bridge and Waterloo roundabout whilst crews continue to work to make the scene safe, so we urge locals to avoid the area."
The brigade was called at 12.48pm and the fire was under control by 1443.
Fire crews from Lambeth, Dockhead, Soho, Brixton, Euston and Whitechapel fire stations attended the scene.
The cause of the fire is under investigation.
The Thirsty Bear – previously the Stamford Arms – was the first pub to introduce self-service ordering with at-seat tablet computers.
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