Aged 15, 18, 38 and 51, the four males were arrested in the city this morning in connection with the violence.
They have been taken to the Serious Crime Suite in Musgrave Station, Belfast where they are currently being questioned by detectives.
The senior detective leading the investigation, Detective Superintendent Jason Murphy, said: “As part of this morning’s operation detectives carried out searches at four houses in the city and arrested four people in connection with the violence which was orchestrated on the streets of Creggan on the evening of Lyra McKee’s murder.
They are currently in custody where they are being questioned.
To date, more than 140 people have provided images, footage and other details to police via their dedicated Major Incident Public Portal.
People with information are still being urged to contact detectives on 101.