NYC 22 follows six diverse NYPD rookies as they patrol the gritty streets of upper Manhattan. The new trainees include Jennifer "White House" Perry, a former college volleyball star and Marine MP in Iraq with a take-charge attitude; Ray "Lazarus" Harper, the oldest rookie and a former police news reporter with better sources than most seasoned cops; Tonya Sanchez, who comes from a family with a criminal history; Ahmad Kahn, an Afghani native who fought his way to freedom; Kenny McClaren, a fourth-generation police officer with great instincts but qualms about joining the force; and Jayson "Jackpot" Toney, a young basketball legend who squandered his opportunity in the NBA. Their demanding Field Training Officer, Daniel "Yoda" Dean, is a case-hardened, unsentimental veteran of the force who emphasizes basics and holds each cop accountable for their actions. Rounding out the team is Sergeant Terry Howard, a no-nonsense plainclothes officer from the Gang Intel Unit, who trains the rookies on how to keep the gangbangers at bay. With unique backgrounds, personalities and reasons for being on the force, the new cops will make their share of rookie mistakes while they figure out how to relate to their boss, each other and the people they swore to protect.
White House and Jackpot try to talk a jumper down from the ledge of a building. Meanwhile, Lazarus and Tonya must locate the parents of a minor involved in a hate crime. Also, a missing dog's owner causes headaches for Kenny and Ahmad.
Lazarus digs deeper when an anonymous Good Samaritan who helped him save a boy from a burning building disappears. Meanwhile, Tonya and Ahmad work undercover on a drug deal, and Kenny and Jackpot find themselves trapped by a live alligator.
Jackpot and White House are first on the scene after a car crash leaves a pregnant woman and her husband trapped. Meanwhile, a plum assignment with a veteran detective isn't what it seems for Kenny and Ahmad, and Lazarus and Tonya guard a raided PCP lab.
Yoda's reminded of his days as a rookie when a drug lord he helped put away is paroled. Tony and Kenny find themselves raiding a house of prostitution. Ahmad and White House come to the aid of a charming con man who's on the run from a loan shark.
Lazarus and Tonya must convince tenants to evacuate their condemned building before the wrecking ball arrives. Meanwhile, Kenny and Ahmad try to find a pickpocket among a group of vendors, and Jackpot and White House patrol a street ball tournament.
Kenny and Ahmad investigate when a bodega owner shoots two men accused of kidnapping his daughter. Meanwhile, recent muggings at a local prep school hit close to home for Lazarus, and White House and Jackpot escort an injured prisoner to the hospital.
A teenage boy creates a bomb and puts it in his backpack, which is switched with a teenage girl's, with Lazarus and McLaren on the case. Sanchez and White House come across a missing child case involving a woman who was once a drug addict wanting back the custody of her son, who is now under the care of a wealthy woman (Samantha Mathis). Jackpot and Ahmad are in charge of a prison transfer, until their transfer vehicle runs out of gas.
Kenny and Ahmad discover there's more to the story when an Ivy League student robs the man who's been mentoring him. Meanwhile, Jackpot and White House are befriended by a young boy, and Lazarus and Tonya try to stop teens from harassing a couple.
White House and Jackpot investigate a man (Richard Kind) who thwarted a bank robbery and uncover more things about the man's life. McLaren's father (Robert John Burke) visits the precinct and discourages him from dating Michelle, T-Rex's sister. Lazarus finally apprehends the wanted man with the shamrock tattoo on his neck, but fears he may face the consequences for not reporting him when he saw him days earlier.
The rookies are assigned their first midnight tour and investigate an explosion that destroyed a neighborhood house where a dope dealer lives. Meanwhile, a rapper shadows Jayson to learn about being a cop for an upcoming movie role.