Trump's son, and the executive vice president of The Trump Organization, Eric Trump tweeted that an electrical fire in a cooling tower was being eyed as the cause.
Trump was in Washington, where he has lived since he was elected president.
People posted video and images to social media, showing smoke rising from the building.
The New York City Fire Department said that the fire started on the terrace and was quickly contained.
NPR said two injuries were reported - a firefighter received a minor injury, and a civilian is "suffering from a serious, life-threatening injury". The fire was believed under control and no injuries were reported, NBC News reported on Twitter.
Numerous fire engines responded to the early morning call at the Fifth Avenue building, with one picture showing more than a dozen vehicles attending the incident.
The first 26 floors host office space.
The building served as Donald Trump's primary residence and workplace before he took up residence in the White House a year ago. The tower also houses a number of businesses.