A seemingly routine murder investigation by the LAPD Robbery-Homicide Division is interrupted by the arrival of Deputy Chief Brenda Johnson, the new head of the LAPD’s Priority Murder Squad. An outsider from Atlanta in her first week of service, Brenda has already begun to face the resistance of long-time high-ranking officers, particularly Capt. Taylor of Robbery Homicide, as well as the questionable confidence of her own squad, who have decided to request transfers en masse. Only her assistant, Sgt. Gabriel, seems willing to try to work with her.

Brenda and the team must investigate the murder of high-profile model Heather Kingsley, who dies as a result of nicotine poisoning, applied to her scalp via her hair conditioner. Suspicion quickly falls on her movie-star husband, Dean, whose philandering ways and false claims of a pre-nuptual agreement make him the likely killer. As Brenda investigates, she is drawn into the world of celebrity beauty, where illusion is everything, and the standard high. When she undergoes a make-over to meet the Dean’s discarded lovers one-by-one, each of whom appears to have a motive to murder, Brenda realizes there may be more to this case than a man trying to get out of a marriage. At the same time, she is slowly seduced by the superficial glamour, which seems to impress her colleagues, and Fritz. As the real killer emerges, Brenda comes to the realization that she can only be who she is, and that the rest is just an illusion.

Brenda must fight for justice for two Russian prostitutes murdered by the illegitimate son of a Russian mafia figure whiles she overcomes the prejudices of a department who sees one dead prostitute as pretty much the same as another. As she does, she confronts her own prejudices, and discovers the justice for these women is scarce in a world dominated by men. When the FBI steps in to take over the investigation, she shows the stern stuff she's made of, using highly unorthodox methods to finally bring the murderer to an unusual form of justice. Meanwhile, Brenda's relationship with Fritz takes a new direction, as the FBI's involvement in this case hints at the challenges that will come when they must balance their work and professional lives. At the end of the episode, Brenda purchases one of the dead girl's house, and finds herself the owner of a cat she doesn't want, but who has ideas of its own.

Brenda and the Priority Homicide Team investigate a sniper who is killing gang members in and around MacArthur Park. Offering assistance is an ex-Army colonel who believes the sniper to be his son. As an all-out gang war looms, Brenda tentatively accepts his assistance, but as her investigation progresses, Brenda's doubts about the Colonel's motives grow. With Fritz' assistance, she realizes the Colonel is not there to help, but to help his son escape. The two face off in the dark on a Los Angeles rooftop, leading to an unexpected outcome. Elsewhere in the story, Sanchez' prior service with the Rampart Division CRASH gang squad allows him to play a pivotal role in the investigation as he briefs the squad on gang activity in the area, goes undercover as a gang member and assists with interrogations. Brenda's tense relationship with Taylor seems to relax, then abruptly grows tenser when a stake-out goes wrong. Gabriel becomes increasingly loyal to her, but Flynn and Provenza continue to resist her methods, dubbing her "Miss Scarlett."

Brenda enters the high-stakes world of pharmaceutical research, when a drug trial for new anti-addiction medication lead to the death of one of the principal investigators. Nothing is quite as it seems as she investigates the high-powered president of the drug company sponsoring the trial, the seemingly easy-going psychiatrist and the teenaged participants in the study. Too soon, one of the teenagers falls victim to manipulation of the medication, and Brenda untangles a web of exploitation of the young victims leading to an unlikely criminal. Meanwhile, Flynn ratchets up his efforts to undermine Brenda's authority, first by going over her head to Pope, and then, when that fails, by unearthing a groundless ethics investigation Brenda faced in Atlanta. On the personal front, Brenda's relationship with Fritz heats up, much to Provenza's delight!

Brenda finds herself the unexpected victim of violence against women when she investigates the murder of a congresswoman's daughter. At first, it appears the victim was engaged in sexual activity online that included an invitation to violence. But as Brenda and the team investigate the world of online solicitation of sex, they discover just how vulnerable to abuse women are, and how easily the web can be used for revenge. In the end, Brenda finds a killer bent on revenge, and saves the victim's reputation, but not without paying a terrible price herself.

When a judge is murdered in Griffith Park, Brenda's investigation takes an unexpected twist. Her best witness, or perhaps her prime suspect, is his teenaged son with autism. Challenged by the boy's behaviors, but convinced he has the clue to unraveling the case, Brenda must try to understand his disability, and thereby learn what he knows. Meanwhile, she must keep his mother, and the child protective system from taking custody of the boy, limiting her access to him, and the killer.

When a gay man is murdered, seemingly the latest victim of a string of hate crimes, Brenda must confront prejudices inside and out of the LAPD. But when the perpetrator of the crimes turns out to be something quite different than expected, and has an alibi for the latest murder, Brenda must dig deeper to discover if this crime is part of the string, or a crime of passion disguised as a hate crime. Meanwhile, Flynn and Taylor step up their efforts to undermine Brenda once again, but with unexpected effects, as the team begins to rally around Brenda. Provenza's quirks begin to emerge, and we meet Terrence Hynes, a County Coroner's Forensics Support worker with an odd sense of humor. On the home front, Brenda finds herself with some new charges when her (male) Kitty has kittens.

Three wealthy, spoiled and unruly children become the target of Brenda's investigation when their stepmother is murdered and the family butler seemingly commits suicide shortly thereafter. Riding heard on the trio is their family attorney, who cleans up their messes and provides them with alibis. Convinced the butler was actually murdered, Brenda sets out to discover which of the children committed the murders, and finds the real killer was someone altogether different!

Brenda finds herself at odds with the FBI in a struggle to gain control of the murder investigation of a well-known businessman. Deciding to work in tandem, Brenda finds herself working directly with Fritz, who was assigned to the case. After discovering that the FBI has ulterior motives in the investigation, Brenda's relationship with Fritz is put under further strain.

Brenda and her team must find not only a killer, but also identify the killer's victim when a deranged, homicidal madman is set free due to mistaken identity. Trying to make sense of an array of complexities in this unusual case, Brenda comes across what may be another betrayal by a member of the Priority Homicide Division. The case takes an even darker turn when Brenda becomes the center of the psychopathic killer's attention.

An unnamed source files a grievance against Brenda in the midst of a high-profile investigation of a murdered L.A. filmmaker. With her career on the line, Brenda is skeptical of Chief Pope's intentions when he volunteers to help. In classic Brenda style, she spurns the accusation, refusing to suppress her demeanor in deference to the complaint. In response to the situation, the PHD team comes together to act in unison, sending shock waves through the entire department.