Ex-government agent and one of the FBI's Most Wanted fugitives, Raymond "Red" Reddington mysteriously turns himself in to the FBI and offers to give up everyone he has ever worked with including a long-thought-dead terrorist but under one condition - he'll only talk to newly-minted female FBI profiler, Elizabeth Keen with whom he seemingly has no connection. For Liz, it's going to be one hell of a first day on the job and what follows is a twisting series of events as the race to stop a terrorist begins.
Red predicts an impending catastrophe, rooted by the work of an assassin, called "The Freelancer." Together, Liz and Red go undercover to prevent from having his next target, Floriana Campo from being killed. Elsewhere, Ressler and newly re-hired CIA agent, Meera Malik, who's been added to Red's private security detail, keep an eye on them from a distance. Meanwhile, Liz considers what she should do next concerning Tom and the mysterious box she found hidden under the floorboards.
The FBI is on the hunt for a high-ranking Chinese spy, Wujing which Red claims has hired him to help decode a classified CIA transmission. Liz, posing as an FBI cryptographer goes with Red to decode the message while protecting US government secrets. Meanwhile, Liz proactively investigates Tom.
While continuing her investigation into the truth about Tom, Liz testifies against drug lord, Hector Lorca. Later another witness is abducted when he is forced to testify against the dangerous drug trafficker. Red's interest is peaked and he informs the team that the witness may have been taken by "The Stewmaker" a man responsible for hundreds of missing and presumed dead people. Meanwhile, in an unlikely twist of events, Red and Ressler must work together for the first time.
Red finds out that The Courier - a middle man that no one crosses - is delivering a package worth millions of dollars to an Iranian spy. Only the Courier is a ghost no one including Red, knows what he looks like. While racing to stop the mysterious criminal transaction, Liz, inadvertently finds herself thrust into a dangerous kidnapping plot. Meanwhile, Ressler must finally accept that Liz is a valuable asset to the team
After Tom confronts Liz about the box - he claims he's innocent and insists that they turn it into the FBI so his name can be cleared. Elsewhere, Red informs Liz and the FBI that the next name on the Blacklist is beautiful and deadly corporate terrorist, Gina Zanetakos.
After a chemical attack on a subway, Liz and the FBI search for the man responsible. Liz reluctantly calls on Red for his help after she finds her search for the next person on the blacklist, brilliant scientist Frederick Barnes, heading to a dead end. Meanwhile, Liz wants nothing to do with Red after he implicated Tom.
Liz uncovers an elaborate plot to destroy the country's financial system when a new name on the Blacklist is revealed by Red. Meanwhile Tom supports Liz when a family member falls ill.
Donald attempts to protect Red from a possible assassination attempt but is misled. The newest member on the blacklist, Anslo Garrick, infiltrates the FBI black site and tries to capture Red. Meanwhile Liz gets caught in an elevator and tries to figure out what is going on.
Liz infiltrates the blacksite and disarms the signal jammers to call in backup but runs into trouble along the way. The fate of Ressler hangs in the balance as Red tries to bargain with Anslo Garrick. Meanwhile, Tom becomes increasingly worried about Liz' situation and the fate of Red is unknown.
The entire FBI team is under investigation as internal affairs tries to find the mole. Elsewhere, Red is missing and conducts his own investigation into who betrayed him. Meanwhile, a serial killer from Liz's past, "The Good Samaritan" strikes again. Liz is allowed to join the hunt for the killer as Cooper knows Red will likely reach out to help knowing how much this unsolved case means to Liz.
Red informs the team that "The Alchemist" - a man who relies upon science to transform a person's DNA - has been contracted to protect a well-known mob informant and his wife. As the team goes undercover to catch him, Liz finds herself on the hunt for an unlikely couple. Meanwhile Liz and Tom find themselves at another bump in their relationship and Ressler debates whether or not he should give his ex-girlfriend his blessing.
Liz and Tom contemplate adoption and after Liz finds out about a illegal adoption agency from Red, she tracks down the CEO of the organization Owen Mallory.
Red reveals a woman from his past, Madeline Pratt is the next target on the list. Liz helps Tom come to terms with their impending adoption. At an elaborate party at the Syrian Embassy, Red manages to convince Liz to pull off a heist.
After been missing for 12 years a prominent prosecutor is found. Red believes a underground judge, Ruth Kipling, is behind the murder and investigates the idea of the killer, previously assumed to of been a myth. The rumors about the myth suggest that a underground criminal appeals process see's those who have wrongfully imprisoned or punished someone in the past, punished themselves. Tom is tempted by a woman at a teachers conference in Orlando and Red does a background check on her.
Mako Tanida a criminal lord and past associate of Red's is next on the blacklist when he escapes from prison. Tom is still annoyed after his mission was interfered with and confronts Jolene about it.
A Russian cyber terrorist known only as Ivan is suspected when a defense asset is stolen online. Liz and Red manage to uncover a huge cover up. New evidence comes to light in the case of Jolene's disappearance which in turn helps in the case of the mystery surrounding Tom.
Red and the team are on the hunt for "The Undertaker" - a life insurance claim adjuster who convinces ordinary people to become contract killers. Meanwhile, Liz works with Red to uncover Tom's secrets.
The Pavlovich brothers specialize in abductions of high value targets and according to Red, they are planning their next hit. While the team tries to protect the next target, Red has a job of his own for the Pavlovich Brothers. Elsewhere, Liz patiently tries to uncover the truth about Tom.
A politician in Prague finds himself being framed for murder, which sees the team attempting to take down the Kingmaker, a strategist who's behind the emergence of some powerful politicians.