Col. Ethan Willis joins the team, bringing new techniques and technologies learned in the field of combat to the hospital; Willis and Mike take a helicopter to Malibu to help shark bite victims; Jesse welcomes new residents.
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.
The doctors treat victims who were caught in a landslide; the entire ER is put at risk when children with measles are brought in.
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 travel to a Russian submarine to treat a sailor who has been wounded in an explosion; the staff at Angels Memorial treats violent criminals who got injured during a prison riot.
The doctors treat the members of a cult who survived a mass suicide attempt; Mario wants to connect with his late father's girlfriend.
Willis, Leanne and Jesse put their lives on the line to operate on an officer with an explosive bullet in her leg; Mario, Noa and Guthrie tend to a magician with breathing trouble.
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.
After Jesse takes a new job at a plastic surgery clinic, he must take one of his patients to Angels when she crashes on the operating table. While in code black, the hospital loses power and the backup generators do not work, as they are still under repair following the boiler room explosion (S.2, Ep.3). While the patients are evacuated to an urgent care facility, Pinkney and Dixon must deliver a baby in the elevator.
Defying Campbell's orders, Leanne uses the hospital helicopter to reunite a family one last time; Willis and Noa find a cellphone app to help them communicate with an autistic girl.
While taking on a new role as the hospital chaplain, Guthrie considers undergoing a risky surgery to treat his Parkinson's; victims of an apartment fire arrive at Angels Memorial Hospital.
Ethan and Mario are asked to attend to two injured construction workers who are trapped on a crane platform 40 stories in the air. Meanwhile, the Angels' staff tends to victims and perpetrators of a school prank gone horribly wrong.
The ER is quarantined when a viral outbreak jeopardizes the lives of the doctors and patients; a young girl whom Leanne bonded with a year ago when she lost her father returns to Angels Memorial.
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.