24 year-old Stanford University Ph.D. candidate Sarah Graiman is set to follow in her genius father Charles' footsteps. Her life takes a dramatic turn when men try to abduct her. She receives a mysterious phone call from KITT, a car of her father's creation, letting her know that her father is in danger. Sarah and KITT set off to recruit her childhood friend Mike Tracer into helping them figure out who has her father and is trying to steal KITT. Mike, having just returned from serving in Iraq, is jaded and reluctant to help, but eventually agrees.
Mike jumps into the thick of a bank heist and tries to stop it, but instead becomes one of the robbers' hostages. Oddly, the robbers do not seem interested in the bank's money. Apparently, they have a specific plan that includes the safe deposit boxes and the husband of one of their hostages. Unable to communication with KITT and his team, Mike tries to enlist the help of the other hostages to stop the robbers from escaping. Unfortunately, one of the so-called hostages is one of the robbers, which makes Mike's job even more difficult.
A plane carrying a 10 year-old federal witness has crashed or so it seems. Mike tries to help the DEA Agent Jessie Renning, by informing her that the crash has been faked and that the drug dealer that killed his father has kidnapped the boy. Considering this information for a brief moment, she instead arrests him for hindering her investigation. Meanwhile, Sarah tries to make a deal with the Deputy Director of National Intelligence for autonomy for the SSC's future cases. Running out of time, Mike and KITT need to find the boy before he is forced to tell where the drugs have been hidden and is killed.
Billy comes along with Mike on a mission to Vegas to bust a money laundering ring, While on the mission Billy is hoping to find romance. Meanwhile, the KITT cave comes under assessment and also locks horns with Dr. Graiman; an old acquaintance.
Mike must stop the spread of a computer virus that threatens a total global meltdown. The job gets much harder when KITT is infected. Meanwhile, Mike’s jealousy begins to show when Sarah reconnects with an old flame, who may be the key to solving the latest mission.
Mike and KITT are trying to track down a stolen serum that maximizes the recipient's physicality before it gets into the wrong hands. With the help of the lab's research assistant, Billy learns some information about the serum that will help Mike when he takes on the now powerful thief. Meanwhile, Sarah is overwhelmed with her new duties and quickly learns how much work it will take to reinstitute the Foundation for Law and Government.
Mike decides to visit one of his old haunts, Sonny's bar, during his decompression time. When Mike arrives, he notices that the crowd has changed for the worse. After learning of Sonny's death in a car accident, Mike is pleased to hear that his daughter Julie is now running the bar. He offers to lend a hand in order to bring the bar back to its original glory. Meanwhile, Mike gets suspicious when he hears of the recent fires at the bar and discovers that someone has secretly being trying to get Julie to sell the place.
Sarah is not coping well with her father's death and decides to leave town. Concerned, Mike goes looking for her and in return gets the answers he has been searching for about his past. Meanwhile, the NSA has decided to dismantle the SSC now that Dr. Graiman is dead and they can then move forward with KITT's nemesis KARR. With Torres' permission they take out KITT's chip that contains his personality and memories and place it in KARR. Upset by what has happened, Mike, Sarah, Billy and Zoe devise a plan to find where KITT has been taken and get him up and running and destroy the evil KARR once and for all.
Knight Industries tracks down a Bonnie and Clyde-esque couple and find that their true identites will affect a congressional race. Meanwhile, Mike and KITT must find a way to save Agent Rivai.
Mike goes undercover as an AWOL Marine in order to find a rogue military officer. A beautiful undercover agent pairs up with Mike to help him solve the crime. Back at the SSC, Billy undergoes training with the help of Zoe.
When a tech is murdered inside of Knight Inudstries, the team must track down the person that infiltrated headquarters before they strike again. Meanwhile, Mike and Sarah find themselves stuck together during a storm.
Mike and KITT must deliver a package, a task that seems easy enough until they learn the package is a man with a code built into his DNA. The task becomes more difficult when a mysterious woman gets in their way.
Mike enlists an old Army buddy to help take down a drag racing gang which is also in the business of arms smuggling overseas. Sarah joins Mike and KITT despite her father's disapproval.
Mike and KITT are sent on an endless string of mini-missions by a crazy terrorist in exchange to keep Ambassador Olara Kumali alive, but they soon realize that they are part of a bigger plan. Trying to outsmart the terrorist, Rivai and a team of FBI agents find themselves in an explosive situation. Meanwhile, Sarah and Dr. Graiman try to fix a sick robot.
Mike's old Army friend recruits his help to investigate the suspicious death of a tough-as-nails drill sergeant Jack Burber. Mike learns that the drill sergeant was participating in an underground fight club for military veterans for extra money. In order to find out what really happened, Mike has to infiltrate the fight club and try not to get himself killed in the ring.
Mike and Zoe go undercover in Baja as a honeymooning surfer couple in order to stop terrorist weapons from getting into the states. Sarah and Billy are brought into the mix and they quickly find the mission taking an unusual turn.
Mike and KITT are now transporting a bomb in the trunk of the car, but in order for it not to explode they must stay above 100 miles-per-hour. Trying to come up with a plan to disable the bomb, they load KITT onto the plane to buy some time and keep up their speed. Clinging to life, Rivai manages to give a clue to find where the terrorist is hiding. Meanwhile, Sarah receives some upsetting news about her dad. Bruce Davison, Yancey Arias and Paul Campbell star. Smith Cho recurs and Rick Hoffman and Richard Roundtree guest star.