First responders in New Haven initially suspected that the drugs were laced with some form of opioid and used Narcan, which combats opioid overdoses, on the patients.
Officials said the patients were "all different ages" and that anti-overdose drugs given to some victims did not work.
Some victims were said to be unconscious while others were vomiting, nauseated or lethargic.
Most were treated at local hospitals, though at least five refused to be transported.
Out of the dozens of people rushed to the hospital, only two showed life-threatening symptoms, authorities said.
Paramedics and police officers assist a man who has just been administered a dose of Narcan for an apparent opioid overdose in Drexel, Montgomery County, Ohio, on August 3, 2017. Some patients were treated multiple times, officials said.
Most of the people who overdosed Wednesday in New Haven were lower-income or homeless, Hartman told WTNH.
EMTs administered Naloxone, an antidote for narcotic overdoses, to some victims but it didn't appear to be effective.
The synthetic drug K2 is suspect to be the reason for these overdoses. "That caused us to respond with a multi-casualty incident", New Haven Fire Chief John Alston said.
Passersby watch in horror as first responders race to treat dozens of people sickened by synthetic marijuana in CT.
"Do not come down to the Green and purchase this K2", New Haven Police Chief Anthony Campbell warned, according to WABC-TV. In May, for example, 25 people were hospitalized in one area of Brooklyn, New York, after having negative reactions to what was believed to be K2, police said.
The overdoses were reported over a 24-hour period and investigators are trying to determine what exactly sickened the victims.
"The substance behind these overdoses is highly risky and must be avoided", Malloy said, adding that state public health officials had delivered 50 doses of Naloxone to New Haven to replenish the supply expended by first responders over the course of the 24-hour crisis. Sandy Bogucki, the EMS and medical director for the Yale-New Haven Hospital region.
"Today's emergency is deeply troubling and illustrative of the very real and serious threat that illicit street drugs pose to health of individuals", Malloy said, according to the Courant.
The slew of overdoses comes as the Centers for Disease Control (CDC) published a preliminary report on Wednesday on the record number of American drug deaths.
A similar mass overdose occurred on New Haven Green just one month ago, on July 4, when more than a dozen people fell sick from synthetic marijuana. It said major causes of the increase in deaths was due to the growing number of people using opioids and that the drugs themselves were becoming more potent.