Police say multiple protesters entered the lobby of the Hilton Garden Inn on Sixth Avenue in Tribeca around 6 p.m.
Witnesses say that at one point, hundreds of people had joined the protest inside and in front of the hotel lobby.
Police gave numerous orders to disperse for 45 minutes, but they did not comply.
Sources told Eyewitness News that at least 66 people have been arrested.
Dante de Blasio was one of the 66 protesters who was issued a summons and released without bail, sources said.
It's not clear if ICE agents are actually staying at the hotel.
Earlier this month, Hilton removed a Minneapolis franchise from its system for refusing to lodge ICE agents.
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