The two 12-year-olds were attacked in Granitehill Road in the Northfield area of Aberdeen about 20:00 on Wednesday.
The area was cordoned off as police and specialist fire crews carried out investigations.
Police Scotland described the suspects as two youths wearing dark clothes and possibly gloves.
The sister of one of the boys posted a picture of him on Facebook, which showed the extent of his injuries.
It showed him with extensive blistering on one side of his face, particularly around his eye.
The post said: "My gorgeous little brothers face! Someone threw some sort of acid/chemical at him and his friends faces!! My poor boy is devastated!"
She later told BBC Scotland her brother was in a lot of pain.
Det Insp Allen Shaw, who is leading the investigation, said: "This has been a shocking and despicable incident against two young boys who have obviously been left upset and shaken by what has happened to them.
"They have been left with significant injuries and were taken to the Royal Aberdeen Children's Hospital for treatment.
"Extensive inquiries are ongoing to trace those responsible and we are working with our colleagues in the Scottish Fire and Rescue Service as part of our investigation.
"There will be a police presence in the area for some time, however the scene where this incident happened has been examined and I can assure the public it is safe.
"I would appeal for anyone with information about the incident, whether you were in the area at the time or know anything about it, to please get in touch.
"You can contact Police Scotland on 101, via the Police Scotland website or via the charity Crimestoppers on 0800 555111 if you would prefer to remain anonymous."
He added: "I can assure the local community that all resources available to us will be used to trace those responsible. It won't be tolerated."
Two young boys have been left with "significant injuries" after chemicals were thrown at them in a "despicable" attack.