At around 1.30am yesterday (Sunday), police were called to reports of criminal damage in Stevenson Square.
Officers attended and established that the George Floyd mural had been damaged.
Following enquiries, officers traced three men nearby who were arrested on suspicion of criminal damage.
They remain in custody for questioning.
Chief Inspector Denise Pye, of GMP's City of Manchester division, said: "This kind of criminal damage is totally unacceptable and will absolutely not be tolerated.
"I understand incidents like this will cause frustration across the district as this behaviour does not reflect our brilliantly diverse and inclusive communities.
"Thankfully officers swiftly attended and following a number of lines of enquiry including CCTV analysis were able to arrest three people in connection with the incident.
"I would encourage any witnesses or anyone with any information to get in touch."
Anyone with information should call police on 101 quoting incident number 253 of 14/03/2021, or the independent charity Crimestoppers, anonymously, on 0800 555 111.
