The new residents are introduced to the ER. A new doctor from the army who knows many advanced procedures is flown to a shark attack on the beach with Mike Leighton and Leighton falls 20 feet from the helicopter. Dr. Guthrie Jr. is promoted to the director of the ER in addition to the OR.

Willis must help a promising soccer player make a life-altering decision after he's seriously injured, and another patient's hesitation to share that she's transgender makes it difficult for the doctors to diagnose her severe abdominal pain.

Willis defies Campbell’s orders when he helps Mario and Heather perform a radical procedure on a maintenance worker stuck under a boiler that exploded. Also, Angus’ father, Dr. Desmond Leighton, tries to seize Power of Attorney over Mike, who is still in a coma, even though Mike granted that right to his brother, Angus.

On Halloween night, Willis, Noa and Elliott rush to the scene of a fire at a haunted theater, where Dr. Nolan and her boyfriend’s son are trapped,

Malaya must inform a college student who regains consciousness at Angels Memorial that she's the victim of a rape. Meanwhile, Willis and Campbell butt heads over a terminally ill woman who wants to end her life on her own terms; and a comedian is treated after he collapses on stage during a performance.

Willis and Campbell are sent to a Russian submarine in U.S. waters to treat a sailor badly wounded during an explosion, and violent convicts injured during a prison riot descend upon Angels Memorial.

The doctors treat cult members who unwillingly survived a mass suicide attempt, and Mario decides to connect with his late father’s girlfriend.

Willis, Leanne and Jesse risk their lives to operate on an injured officer who has an explosive bullet lodged in her leg. Meanwhile, Mario, Noah and Guthrie treat a magician who comes to the hospital with breathing difficulties.

A 13-year-old girl arrives at Angels Memorial following a seizure caused by spina bifida and the doctors are shocked to learn she is Campbell's daughter. Meanwhile, a workaholic deaf patient and her translator are treated after their car rolls into the Los Angeles River.

A code black at Angels Memorial takes a turn for the worse when a city- wide blackout leaves the hospital without power or back-up generators. As Campbell and Leanne divert high-risk patients to a nearby care center, Elliot and Heather are trapped in an elevator with a woman in labor, and Willis and Dr. Nolan try to help a 92-year-old woman who thinks it’s 1942.

Leanne defies Campbell's order and uses the hospital helicopter to reunite a family for the last time. Meanwhile, Willis and Loa use a cell phone app to communicate with an autistic young girl.

Guthrie becomes the hospital's new chaplain and considers undergoing a risky surgery to treat his Parkinson's. Meanwhile, the doctors treat patients involved in an apartment fire.

After pulling a double shift, Mario risks his own life when he follows Willis to a construction site where two brothers are trapped on a crane 300 feet above the ground.

The ER is quarantined when a viral outbreak jeopardizes the lives of the doctors and patients at Angels Memorial. Also, Ariel, the young girl Leanne bonded with a year ago when she lost her father, returns to Angels.

The doctors work with the Center for Disease Control and Prevention to find an antidote to the deadly viral outbreak at Angels Memorial. Also, Leanne makes a life-changing decision, and Jesse welcomes a new batch of residents.