The mural was painted in front of Trump Tower last week to send a very clear message to the president. That message has created strong emotions.
On Monday night, cellphone video surfaced showing a man in daylight but partially disguised with a mask and hat splashing red paint on the mural, then running away.
Mayor Bill de Blasio addressed the incident on Twitter.
"To whoever vandalized our mural on 5th Avenue: nice try. @NYC_DOT has already fixed it," the mayor wrote in part.
Crews restored the mural Monday.
"We're sitting here today in 2020 and we have to go through something like this. It's a shame. It's deplorable," one man said.
"This just agitates more and more people, without any real substance to it, at this point," another person said.
This comes after a weekend of altercations between "Back The Blue" pro-police protesters and Black Lives Matter sympathizers.
On Sunday, a fight erupted in Bay Ridge, Brooklyn, where five people were arrested and charged, including a 41-year-old man who was Tased by police. Charges against him are pending.
The incidents have deepened the nationwide controversy over police reform.
"There is no justice without safety and there is no safety without justice. The mere fact someone critiques problem policing is not an attack on law enforcement," said Brooklyn Borough President Eric Adams.
Adams spent much of his career as an NYPD officer. He's going to begin a series of conversations between Black Lives Matter and the police.
"If a bullet leaves a barrel of a gun, it does not discriminate if it hits an officer in a blue uniform or a young man in blue jeans, or a little baby 1 years old in a blue baby carriage," Adams said.
Adams says you can support the police and still believe the department needs reforms.
As gun violence continues to plague the city, Adams said there has to be a sense of urgency to finding common ground.
Police said the mural defacing investigation is ongoing.