The victims’ bodies were discovered after a friend of the group returned to the building in the north of the city at around midday on Saturday.
All five are adults but detectives did not release any information about their ages, genders or causes of death.
“We can tell they are homicides,” said St Louis County police officer Tracey Panus outside the scene on Chambers Road.
“We got a call around noon for suspicious deaths in the 1900 block of Chambers. When we responded we found five deceased victims.
“We don’t know cause of death, we don’t have any suspects in custody, we are just looking for tips, we are looking for people to call our investigators to provide any information they may have seen between 9pm and noon today.”
Detectives used specialist equipment to take 3D images of the crime scene as part of the homicide investigation.
The St Louis Post-Dispatch newspaper reported that the bodies were discovered by the father of one of the victims.
Ronald Brewster, 68, said he went to the apartment to pick up his 40 year-old son, also named Ronald, for a family reunion. He said his son was a drug user, adding: “I worried about him and tried many times to get him into rehab.”
Photographs of the single-floor apartment block showed several windows and doors boarded up. Police said not all of the units were vacant.
St Louis County Police chief Jon Belmar said: “It’s a tragedy for a community, any time there is a scene like this, when five individuals are a victim of homicide.
“We need help from the community to assist us - somebody out there knows what happened.”