The latest violence underscored the urgency to get the homeless off the streets and into safe housing, said Jacquelyn Simone, policy director for the Coalition for the Homeless in New York City.
"These people were attacked because they didn't have that safety of permanent housing," she said. "That's why we need to use these tragedies as an opportunity to redouble our efforts to ensure people have a better option than the streets where they're exposed to both the elements as well as people who might wish to do them harm."
Simone and other advocates for the homeless called on the city to use vacant hotel rooms for temporary shelter for those who would rather stay on the streets rather than opt-in dormitory-style housing.
The earliest known shooting was at around 4am on March 3 in Washington DC, police said, when a man was shot and wounded in the city's Northeast section. A second man was wounded on March 8, just before 1.30am.
At 3am the next day, March 9, police and firefighters found a dead man inside a burning tent. A subsequent autopsy revealed that the man had died of multiple stab and gunshot wounds.
The killer then apparently travelled north to New York City, police said.
At 430 early on Saturday morning, a 38-year-old man sleeping on the street in Manhattan not far from the entrance to the Holland Tunnel was shot in his right arm as he slept.
The victim screamed and the gunman fled, police said.
About 90 minutes later, the gunman fatally shot another man on Lafayette Street in SoHo, police said. The man's body was found in his sleeping bag just before 5pm on Saturday.
Police determined the same person committed the attacks based on the similarities of each shooting and evidence recovered from the scenes. The victims were attacked without provocation, police said.
"We are committed to sharing every investigative path, clue and piece of evidence with our law enforcement partners to bring this investigation to a swift conclusion and the individual behind these vicious crimes to justice," Metropolitan Police Chief Robert Contee said in a news release.
The federal Bureau of Alcohol, Tobacco, Firearms and Explosives is assisting in the investigation.
The attacks were reminiscent of the beating to death of four homeless men as they slept on the streets in New York's Chinatown in the fall of 2019. Another homeless man, Randy Santos, has pleaded not guilty to murder charges in those attacks.
A year ago, four people were stabbed in New York City, two fatally, by a man who randomly attacked homeless people in the subway system. That assailant, who was also homeless, is awaiting trial.
Mayor Adams has come under fire for his plan to remove homeless people from the city's subway system by deploying police and mental health workers to keep people from sleeping on trains and subway stations.
Advocates said the policy was misguided and unfairly criminalised people who were down on their luck or who weren't getting the help they needed to steer them back into permanent housing.
Adams has said homelessness was a complicated issue, exacerbated by the pandemic, the economic downturn and mental health challenges.
New York Governor Kathy Hochul has said the state was working to get more psychiatric beds at hospitals available by increasing the amount of money hospitals receive for having the beds.