The incident occurred in the Earlscourt housing estate on the Dunmore Road at around 11pm on Thursday night.
Gardaí believe some type of chemical was thrown which resulted in three people being injured.
One of the youths has been treated in University Hospital Waterford for a serious eye injury, the others had injuries to their hands.
In some instances the fluid had burnt through clothes and onto the skin.
The 16, 17, 18 and 19 year olds were arrested at different times on Saturday and questioned under section 15 about violent disorder.
Gardaí have carried out house to house inquires in the area and the investigation is ongoing.
They're appealing to members of the public, parents and teenagers who may have information or social media footage to contact Waterford Garda Station on 051 305300.
