In the season premiere "Mayhem", Sienna Guillory and Erik Palladino reprise as SSA Kate Joyner and Detective Cooper, respectively. Adoni Maropis guest-starred as Ben Abner, a member of the NYC Terrorist Cell who disguises as a paramedic, and Michael Steger guest-starred as Sam, another member of the cell. In the episode "The Angel Maker", Lauren Bowles guest-starred as Chloe Kelcher, the copycat killer and love interest of Courtland Bryce Ryan, aka "The Angel Maker", played by Neil Hopkins. Blake Lindsley guest-starred as Shara Carlino, another attempted copycat and admirer of Ryan. In the episode "Minimal Loss", Luke Perry guest-starred as Benjamin Cyrus, the leader of a religious cult known as the "Separatarian Sect". Jeff Fahey guest-starred as Leo Kane, an inmate and fervent libertarian who founded the Liberty Ranch. In the episode "Paradise", William Mapother and Robyn Lively guest-starred as Ian and Abby Corbin, a married couple who go on vacation, only to be held captive by Floyd Hansen.
In the episode "The Instincts", Melinda Page Hamilton guest-starred as Claire Bates, a child abductor who kidnaps a young boy. In the episode "Memoriam", Taylor Nichols guest-starred as Spencer Reid's father, William, who confesses to murdering Gary Michaels, a pedophile who intended to rape and murder Reid after he already raped and murdered another young boy. Dee Wallace guest starred as Reid's therapist, Dr. Jan Mohikian. In the episode "Masterpiece", Jason Alexander guest-starred as Henry Grace, a serial killer obsessed with the fibonacci sequence. In the episode "52 Pickup", Gabriel Olds guest-starred as Robert Parker, a serial killer who has perfected his skills as a pick-up artist. Courtney Ford guest-starred as Austin, a bartender who develops a crush on Reid. Currie Graham guest-starred as Paul "Viper" Thomas, another pick-up artist who was a suspect in the murders, and Joanna Cassidy guest-starred as Mrs. Holden, a woman whose youngest daughter Vanessa, is murdered by Parker.
In the episode “Brothers in Arms”, Mark Pellegrino guest-starred as Lt. Evans of the Phoenix, Arizona police department. Guillermo Díaz guest-starred as gang member and suspect Playboy, and Doug Jones appeared as fight club captain Beanie. In the episode "Normal", Mitch Pileggi guest-starred as Norman Hill, aka "The Road Warrior", a man who goes on a murderous rampage after murdering his entire family. Faith Ford guest-starred as Norman's deceased wife, Vanessa, and Gina Torres guest-starred as Detective Thea Salinas, who leads the investigation of the murders. Elaine Hendrix guest-starred as one of Norman’s victims. In the episode "Soul Mates", George Newbern and Michael Boatman guest-starred as Steven Baleman and William Harris, aka, "The Soul Mates", a duo of serial rapists who murdered several women. Dana Davis guest-starred as William's daughter Andrea. In the episode "Bloodline", Andrew Divoff and Cynthia Gibb guest-starred as Lewis and Kathy "Sylvia" Gray, a gypsy couple who abducted young girls for their son to marry by the time he comes of age.
In the episode "Cold Comfort", Vondie Curtis-Hall guest-starred as Stanley Usher, a self-proclaimed psychic of whom David Rossi is skeptical, and Cybill Shepherd as Leona Gless. In the episode "Zoe's Reprise", Amy Davidson guest-starred as Zoe Hawkes, an admirer of Rossi who aspires to become an FBI agent, only to be murdered by Eric Olson, played by Johnny Lewis. Shannon Woodward guest-starred as Eric's girlfriend, Linda Jones. In the episode "Pleasure Is My Business", Brianna Brown guest starred as Megan Kane, a call girl who fatally poisons her clients. In the episode "Demonology", Carmen Argenziano guest-starred as Father Paul Silvano, an Italian priest who murders his victims through exorcisms. Bruce Davison guest-starred as Father Jimmy Davison.
In the episode "Omnivore", C. Thomas Howell guest-starred as George Foyet, the only person who survived a string of killings committed by a killer known as "The Boston Reaper". Louis Ferreira guest-starred as Roy Colson, a novelist and the author of the novel Night of The Reaper. In the episode "House on Fire", Tommy Dewey guest-starred as Tommy Wheeler, a serial arsonist who burns down a movie theater, killing everyone trapped in it. Shannon Lucio guest-starred as Tommy's sister Tina. In the episode "Conflicted", Jackson Rathbone guest-starred as Adam Jackson, a delusional serial killer who has a female alter-ego named Amanda. Susan Ward guest-starred as Julie Riley, a hotel manager who was suspected of committing the murders of several men. Roma Maffia guest-starred as Detective Reese Evans, who leads the investigation of the murders.
In the episode "The Big Wheel", Alex O'Loughlin guest-starred as Vincent Rowlings, a repentant serial killer who suffers from uncontrollable homicidal urges. In the episode "Amplification", Tamlyn Tomita guest-starred as Dr. Linda Kimura, who aids the BAU with the investigation of an anthrax outbreak that has infected several people. In the two-part season finale "To Hell and Back", Garret Dillahunt guest-starred as Mason Turner, whose developmentally disabled brother and partner in crime, Lucas, abducts a teenage girl and holds her captive at a barn in Canada. C. Thomas Howell reprises as George Foyet, who breaks into Aaron Hotchner's apartment and seemingly shoots him. Hotch's fate is left unknown until the premiere of the following season.
When a bomb placed under a government-owned SUV detonates in New York City, the BAU tries to determine if one of their own was injured and apprehend the people responsible before a larger-scale incident occurs.
When a series of murders take place on the one-year anniversary of an Ohio serial killer's execution, the BAU determines that a copycat is attempting to finish what the original killer started. Meanwhile, Hotch struggles to recover from a debilitating injury.
When authorities in La Plata County, Colorado receive a 911 call alleging child abuse at a compound belonging to a religious cult, Prentiss and Reid go undercover to investigate only to find themselves embroiled in a high-stakes hostage crisis after a raid goes disastrously wrong.
When three unrelated car accidents in Nevada are revealed to have been staged, the BAU attempts to catch an unsub who psychologically torments traveling couples before he has a chance to kill again.
When a series of robbery-homicides in California's Central Valley claim the lives of six people, the BAU determines the killer chooses his victims based on their proximity to the railway. Meanwhile, JJ introduces the team to prospective temporary replacement Jordan Todd (Meta Golding).
When a five-year-old Las Vegas, Nevada boy is found dead and another boy is abducted soon afterwards, the BAU attempts to find a common demoninator between the crimes. Meanwhile, Reid starts suffering from recurring dreams that force him to recall forgotten childhood memories.
Reid decides to stay in Las Vegas in an attempt to determine whether or not his estranged father is responsible for the murder of a childhood friend. Meanwhile, JJ goes into premature labor and gives birth to a son.
When a narcissistic psychopath obsessed with the Fibonacci sequence confesses to killing seven people and claims that five more will die, the BAU attempts to locate his latest victims before time runs out. Meanwhile, Todd struggles to deal with the fact that the team does not yet trust her.
When several Atlanta, Georgia women are disemboweled and left to bleed to death, the BAU determines that the killer is a man who uses his social charm to lure potential victims to their death. Meanwhile, Todd's working relationship with Hotch is tested following a misleading encounter with one of the victims' families.
When several members of the Phoenix Police Department are shot and killed in the line of duty, the BAU juggles gaining the department's trust and building a profile as they set out to catch a killer whose ruthlessness is matched by his determination.
When three Orange County, California women are gunned down, the BAU sets out to catch an emasculated spree killer before he can strike again. Meanwhile, Todd makes a decision that causes her to reevaluate her new position and JJ and her son pay a surprise visit.
After arresting a Sarasota, Florida family man for the abductions and murders of several young women, the BAU works with his daughter in an attempt to determine the identity of his partner and prevent him from killing another woman.
When a Harvest, Alabama couple is stabbed to death in their home and their daughter is abducted, the BAU determines the crime was committed by a Romani family enacting a ritual aimed at acquiring wives for growing sons.
With JJ back from maternity leave, the BAU travels to Olympia, Washington to identify a serial killer who murders and embalms young women. Meanwhile, Rossi comes into conflict with a psychic hired by the latest victim's mother.
While investigating a series of seemingly unrelated murders in Cleveland, Ohio, the BAU determines a copycat killer is recreating murder techniques used by past serial killers. Meanwhile, Rossi becomes personally involved in the case after learning that the latest victim was a criminology student who tried to bring the case to his attention.
When two Dallas, Texas corporate executives are poisoned while staying in high-end hotels, the BAU juggles searching for a call girl with a sinister vendetta and convincing the victims' lawyers to cooperate.
When three men in the Washington metropolitan area are found dead under suspicious circumstances, the BAU determines that a Catholic priest deliberately subjected all three victims to fatal exorcisims. Meanwhile, Prentiss becomes emotionally involved in the case after learning that one of the victims was a childhood friend.
When a New England serial killer resurfaces after a ten-year absence, the BAU sets out to catch him before he can pick up where he left off. Meanwhile, Hotch becomes personally involved in the investigation when the former lead investigator reveals a stunning secret.
When an escalating serial arsonist kills nineteen people at an Indiana movie theater, the BAU attempts to determine his identity and prevent him from setting another fire before he can strike again.
When two male college students are sexually assaulted and fatally suffocated while vacationing in South Padre Island, Texas, the BAU finds themselves forced to rethink their initial theories of a two-person team after an unexpected twist to change the course of the investigation.
While investigating a series of child abductions and murders in Cherry Hill, New Jersey, the BAU uncovers a horrifying truth after noticing several differences between the most recent disappearance and the first two murders.
When authorities in Buffalo, New York receive a video showing a man stabbing a real estate agent and subsequently writing a plea for help, the BAU sets out to catch an obsessive-compulsive who has killed several women over the last ten years.
When four fatal hit-and-runs take place in Bend, Oregon, the BAU determines the victims were targeted by a killer seeking revenge. Meanwhile, Garcia finds herself forced to make a personal decision after Kevin reveals the NSA is interviewing him for an overseas position.
When twelve people die from a modified strain of anthrax in Annapolis, Maryland, the BAU works with the U.S. Armed Forces to identify the perpetrator before he stages another attack. Meanwhile, the team becomes emotionally involved in the case after one of their own is exposed to the strain.
When an Iraq War veteran goes to great lengths to convince authorities to find his missing sister, the BAU sets out to catch a serial killer who abducts homeless people from Detroit, Michigan and smuggles them into Canada for a twisted agenda.
After identifying two Ontario brothers as the perpetrators behind the disappearances of over eighty people, the BAU juggles profiling the siblings and preventing their latest abductee from meeting a gruesome fate. Meanwhile, a killer from the team's past prepares to exact vengeance against one of their own.