The blast, which wounded 29 people, and the discovery of a pressure cooker device set the city on edge on what should have been a vibrant night on Manhattan's west side.
At the late night news conference where city authorities announced their initial findings, O'Neill, 59, 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 on Friday -- Bratton's last day on the job.
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.
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O'Neill has 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, CNN commented.
O'Neill has said he will focus on reconnecting the police force and residents.