President Trump was not in the building, and nobody inside it was evacuated.
Video footage shared on social media smoke billowing from the top of the 58-storey building.
Emergency responders told CBS News that the fire began in a ventilation shaft.
Firefighters are on the scene along with members of the NYPD.
Two civilians and a firefighter were treated for non-life-threatening injuries, the department said.
Eric Trump, the president's son, said there was a small electrical fire in a cooling tower on the rooftop and that the fire department arrived at the scene within minutes.
The Fire Department of NY says the fire started around 7 a.m. Monday at the building that contains U.S. President Donald Trump's home and business offices. The fire was believed under control and no injuries were reported, NBC News reported on Twitter. It serves as the headquarters for the Trump Organization and is located on Fifth Avenue between 56th and 57th Streets.
The president, who has a penthouse residence in the tower, as well as business offices there, is not believed to be at the midtown, Manhattan tower block at this time.
A call came in just before 7 a.m. for a blaze at 721 Fifth Ave., which is the skyscraper where President Donald Trump lived before moving to the White House previous year.
Fire crews are responding to a fire at Trump Tower.