The series revolves around Walter White, a 50-year old high school chemistry teacher living in a suburb of Albuquerque with his pregnant wife Skyler and his teenage son Walter Jr., who has cerebral palsy. A brilliant chemist, Walter is depressed and bored with the way his life has turned out, which among other things has him financially strapped to the point of having to take a second job as a cashier at a local car wash. When Walter suddenly collapses at work one day, Walter is taken to the hospital and discovers that he has terminal lung cancer and two years left to live at best. The revelation causes a change in Walter, making him more agressive, as he quits his second job and beats up a bunch of teenagers who mock his son when the family are out shopping. Ultimately Walter contacts his loutish brother-in-law Hank, a DEA agent who leads a local SWAT Team Unit) about tagging along with him on an upcoming raid after being offered a chance to watch the group in action earlier.

As they stake out the suspected house, Hank says their target is a big meth dealer known as "Captain Cook." The SWAT team bursts into the meth lab and arrest someone named Emilio who they think is Captain Cook. When Hank and his partner leave Walter in the car to inspect the scene, Walter notices a half-dressed young man escape out the top floor window next door unnoticed by SWAT, leaving a topless woman behind. Walter and the young man immediately recognize each other - he is Jesse Pinkman, Walter's student from many years ago. Jesse escapes unseen by SWAT in his car, which has the license plate "THECAPN," which means that he is actually the man Hank was looking for.

Walter does not tell anyone about Jesse, but tracks him down on his own. Walter proposes that he becomes his new "cook," as Emilio was the one who knew how to make the meth. With his chemistry knowledge, Walter offers to help make high quality crystal meth that would make both men a lot of money. Acquiring a RV, the two men drive to the middle of the desert, and cook there. After a run in with Jesse's former drug dealer associates (Krazy-8 and Emilio), the two men are held captive until Walter attempts to kill Krazy-8 and Emilio by exposing them to phosphine. Walter notices that a brush fire has started from Emilio's cigarette that had been tossed out of the RV, Walter dons a gas mask and puts another on Jesse, dragging him into the RV and driving away from the fire. As sirens blare off in the distance, Walter attempts (and fails) at committing suicide, as the sirens turn out to be fire trucks headed for the brush fire; they pass Walter and Jesse without showing any interest in their situation.