The blast, which wounded 29 people on Saturday night, and the discovery of a pressure cooker device set the city on edge on what should've been a vibrant night on Manhattan's west side.
At the late night news conference where authorities announced their initial findings, O'Neill took the mic to reassure residents the NYPD was on full alert and an investigation underway.
But his was an unfamiliar face to most. Saturday marked his first full day on the job as the city's 43rd commissioner, succeeding William Bratton. O'Neill was sworn in Friday -- Bratton's last day on the job.
So just who is the man who oversees the largest police department in the United States?
He's a long-time police veteran
O'Neill has over three decades of experience with the force, first beginning his career in 1983 with the transit police.
"He credits his time on patrol on the trains and platforms of the subway system with helping him learn how to interact and communicate with a wide range of people, a skill he regards as essential to successful police work," the NYPD website says.
He gradually rose through the ranks, including as commanding officer of the 25th, 44th and Central Park precincts, followed by chief of patrol. In 2014, he was named chief of department, the NYPD's highest uniformed rank, before replacing Bratton.
He's from New York
Flatbush, Brooklyn to be exact. He grew up as one of seven children, later attending John Jay College.
He's known to go by "Jim" or "Jimmy."
He has two sons, Daniel and Christopher, and is described by the NYPD as an "avid hockey player and motorcyclist."
Crime down but challenges ahead
He's inherited a record low crime rate, thanks to Bratton's tenure, but will have to grapple with other significant challenges, especially surrounding issues of race and terrorism.
O'Neill has a demonstrated track record when it comes to racial relations. He pioneered the idea of neighborhood policing, or building relationships between police officers and the community to increase trust -- and not long after stepping up to Chief of Department, he handled the protests around Eric Garner's death
and the subsequent assassinations of two detectives.
He's said he will focus on reconnecting the police force and residents.
"Fighting crime is what we get paid to do," O'Neill said, according to the NYPD website. "But we can't do that unless we achieve full partnership with the community. Unless we have that connectivity, it's not going to work."