The hotel says it is "aware of a situation".
The London Ambulance Service sent multiple crews to the scene shortly before 4pm on 6 June including a hazardous area response team.
Images from the scene showed vast plumes of black smoke billowing from the building into the London skyline.
"The cause of the fire is not known at this stage".
Overlooking London's Hyde Park on one side and Knightsbridge on the other, the property was originally built in 1889 as an exclusive "Gentleman's Club".
It was the sort of smoke you get when there is a chip pan fire. She speculated that a construction site on the hotel's roof had caught fire.
The historic, Edwardian-style building was first opened as the Hyde Park Hotel in 1902 before it was bought by Mandarin Oriental Hotel Group in 1996.
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Firefighters tackle a blaze at the Mandarin Oriental Hotel in central London on Wednesday.
The hotel boasts a stunning spa and world-famous restaurants including Michelin star signature restaurant Foliage.
In a statement, the London fire brigade said: "The brigade was called at 3.55pm".
Penelope Evans, 50, from Battersea, south London, was shopping in Harrods when she noticed the thick smoke. In a press release announcing the completion of the project last week, the Mandarin said the rooms were were "now more luxurious and comfortable than ever before".
Jack Martin, a 21-year-old student from Peckham, said he was coming out of Knightsbridge station when he saw a "huge billow of smoke". "Everything's fine but we don't know how it started yet", a person present at the spot said.
The road in front of the five-star hotel in London's ritzy Knightsbridge neighbourhood was closed, causing rush-hour traffic chaos in the area. It underwent a complete renovation in the late 1990s, and reopened to the public in May 2000.
The Queen hosted an event at the Mandarin Oriental for British and foreign royals ahead of the wedding of her grandson Prince William to Kate Middleton in 2011.