When a fire claims one of their own, there's plenty of guilt and blame to go around. Lt. Matthew Casey, in charge of the Truck, tries to carry on, but butts heads with the brash Lt. Kelly Severide of the Rescue Squad - and each blames the other for their fallen team member. The firehouse also includes: Battalion Chief Wallace Boden, a fireman's fireman who is confronted by important personal decisions; paramedics Gabriela Dawson and Leslie Shay, who share a close bond and team together to face some of the most harrowing situations imaginable; Peter Mills, an academy graduate who is the latest generation in a family of firefighters; and Christopher Herrmann, a seasoned veteran who loses his home to foreclosure and now must uproot his family to move in with his in-laws.

Severide is hiding a serious shoulder injury sustained in the fire that killed Andy Darden, and grapples with his guilt as he fights to rescue a construction worker trapped in a building collapse. Adding to the burden, Darden's wife Heather turns on Severide at the annual firefighters' barbecue, blaming him for her husband's death. A call is made to an accident site at Hancock Tower, where two teenagers are pinned in a vehicle trapped beneath the falling debris of a broken window washer's cart. Meanwhile, Casey and Hallie work to figure out their future together.

Casey faces pressure to cover for a cop's son, who was responsible for a drunken-driving accident that left a teenager paralyzed. Meanwhile, Severide ignores his doctor's warnings that his neck injury may never heal if he doesn't seek treatment; and Mills must choose between working at the fire department full-time or helping his mom with her restaurant.

Chief Boden is accused of leaving a homeless man to die in a warehouse fire after ordering his men to evacuate the scene, creating negative press and bad feeling within the department. Meanwhile, Lieutenant Severide helps an elderly woman facing some neighborhood problems. Detective Voight ramps up his intimidation tactics aimed at Casey in an attempt to discourage him from testifying against his son. Shay is forced to revisit her heartbreak over her ex-girlfriend Clarice, when she finds herself face-to-face with the ex and her husband during a call. Hermann’s temper flares during a rescue call at a Halloween block party.

Casey confronts Detective Voight about his harassing tactics, vowing never to back down, and ends up paying the price for his decision. Dawson faces disciplinary action for her on-the-job conduct. Meanwhile, Severide finds his arm failing him during a rescue at a construction accident, and reaches out to Anna, an old flame and pharmaceutical rep, hoping she might be able to help alleviate his injury problems.

Facing suspension, Dawson gets a hand from the same girl she saved through the procedures that landed her in front of the disciplinary board. Lieutenant Casey finds his fuse shortening as Detective Voight stops at nothing to get him to retract his statement. However, when Casey lays his life on the line during an apartment fire, he may have unknowingly caught the break he was needing.

Everyone in the firehouse is ordered to take a drug test after a call to a daycare center exposes them to a makeshift meth lab, and Severide stalls, not wanting his injury, or the painkillers he takes, to be discovered. Meanwhile, Truck and Squad find themselves pinned down by gunfire while trying to help the victim of a gang shooting, and a deep-fried turkey fire grows from small to explosive when a garage catches fire. Elsewhere, Dawson saves a bleeding man and Casey delivers a baby on the scene of a massive car pileup on the freeway.

At the site of a train accident, Peter Mills becomes deeply upset when he observes the dead body of a young victim. Unable to shake his emotional distress about the event, he questions his future as a firefighter. Dawson and Shay save a 6-year-old girl whose mother is abusing her – but their confrontation leads the woman to resort to dire actions. Meanwhile, Severide aggravates his injury while rescuing a heart attack victim and Shay sends Clarice, her married, pregnant ex-girlfriend, back home to her husband.

After he's injured in a terrible fire at an auto machine shop, Jose Vargas is forced to go on disability and leave his life as a firefighter behind - a task he finds incredibly difficult. Chief Boden tries to help a suspected teenage firebug. Also, Severide receives an enticing invitation from Renee, a woman who he saved from a car crash incident involving live electrical wires. Meanwhile, Cruz tries to save his younger brother Leon from the gang he is involved with.