Raymond "Red" Reddington is one of the FBI's Most Wanted, a criminal mastermind known as "The Concierge of Crime," a man without a country or political agenda. Despite their best efforts, the FBI hasn't come close to catching Reddington in years, which is why his puzzling and conspicuous surrender at FBI headquarters is met with a wide range of skepticism. What's the catch? Red has an offer: He will help the FBI get their hands on Ranko Zamani, a high-value terrorist thought to be dead for years, but he will work only with profiler Elizabeth Keen. Unfortunately for the FBI... it's her first day on the job.
The FBI brings Liz in to speak with Red; she's a rookie with a sense of bravado and uncanny talent for what she does. Red thinks he knows her, but they both have a lot of learning to do about one another. Red tells Liz that Zamani is planning to kidnap a U.S. general's daughter within the hour. The FBI rushes into action, and though Elizabeth was supposed to attend an adoption agency interview with her husband Tom, she's forced to cancel, as "something classified has come up."
Led by Agent Donald Ressler, the FBI rescues the general's daughter, Beth, from her ballet class and attempts to extract her to a safe location. But Zamani is two steps ahead of them, and the FBI convoy drives right into an ambush on a D.C. bridge. Disguised as HAZMAT workers, Zamani's men pull off a daring and complicated operation to abduct Beth, leaving Keen bloody and most of her co-workers dead. Back at the defunct post office where Red is chained to a chair in an elaborate mechanized cell, the FBI asks him to come up with a strategy for rescuing the General's daughter. He insists they stop thinking like cops and start thinking like criminals. Liz realizes Zamani is trying to settle a personal vendetta against the General over a bombing that killed his family years ago. Liz thinks Zamani is planning to exact revenge by detonating a bomb in the D.C. area... using Beth as the detonator.
Red knows where Zamani's bomb chemist is, but in exchange for the information, he demands the FBI unshackle him and house him in a penthouse suite in one D.C.'s finest hotels; after all, if they expect terrorists to deal with him, people must think he's out and about on his own free will. The FBI reluctantly agrees and eventually tracks down the chemist. When Liz goes home to clear her head, she finds her husband tied to the kitchen table, bloody and beaten. Zamani enters, demanding she explain how much she knows about his plan. She begs him to leave Tom alone and says she knows little more than her suspicions about a bomb. Zamani offers a deal: Liz can stop him now and save many, or she can try to save one. He stabs Tom in the stomach and runs away, leaving Liz in a panic, trying to save the life of her husband.
With Tom in a coma, Liz proceeds to Red's hotel in a rage to accuse him of sending Zamani to her house, underlining her point by stabbing Red in neck - the carotid artery - with a pen. If he doesn't reveal everything he knows about Zamani immediately, she'll let him die right there at the table. The FBI places Liz under official review for this assault, but she's brought back into the fray when Red escapes from his hospital bed. The FBI initiates a manhunt. Red meets Zamani at the Lincoln Memorial to discuss the terror plot. It's unclear where Red's allegiance lies, but Zamani intimates Red was involved in the attack on Tom. As the FBI tracks him down, Red calls Liz and asks her to think critically about her interaction with Zamani... to recall details. She struggles at first, but eventually realizes Zamani had a stamp on his hand. It's the stamp for the D.C. Zoo.
Liz finds Beth at the D.C. Zoo, the bomb strapped to her in an inconspicuous backpack. Meanwhile, Red extracts the GPS implant the FBI placed in his neck and gives it to Zamani. The FBI kills Zamani on top of a nearby skyscraper just as a Ukrainian criminal pops up at the zoo to dismantle the bomb on Beth's back. To keep Beth calm, Liz talks about the scar on her hand, saying she got it from her father and it always reminds her to be brave. Beth touches the scar, hoping it can make her brave as well. As the Ukrainian stops the bomb and runs off with it, Red shows up to explain the bomb is payment for the Ukrainian's services. Just then the FBI swarms them and Red peacefully gives himself up once more.
The FBI is all but done with Red until he lets them know Zamani is just one name on an entire list of criminals, politicians and terrorists he's been compiling for over 20 years. It's his "Blacklist"; it's all in his head and he's willing to share with the FBI, but only if... Red's demands are outrageous, but the FBI reluctantly takes the bait. Back at her place, a distraught Liz scrubs Tom's blood out of the carpet. Frustrated, she rips the carpet up to find something disturbing: under the floorboards is a box full of assorted passports featuring Tom's photo, a big pile of money and a gun...