Kathryn Morris stars as Philadelphia homicide detective Lilly Rush, who investigates long-unsolved crimes, otherwise known as Cold Cases. In the pilot episode, Lilly investigates a 1976 case involving a teenage girl who was beaten to death on a tennis court during a party at a plush estate. A maid to a wealthy family, Bonita Jakarta (Lillian Hurst), claims she witnessed the murder of teenager Jill Shelby (Kate Mara). Now dying of cancer, the maid who remained silent, wants the killer brought to justice. Rush reopens the case, in which two brothers were originally suspected but not charged due to their powerful society family. Lilly interviews several witnesses: Jill's best friend Melanie (Lisa Waltz), and her boyfriend, Todd Whitley (D.W. Moffett) (who is now married to Melanie) and his troubled brother Eric (Michael Reilly Burke). The evidence points mostly to Eric, now a troubled alcoholic, but lawyer Todd has secrets of his own. Determined to uncover the truth, Lilly must force the Whitleys to confront their dark past despite resistance from everyone involved in the case, including the victim's mother (Elizabeth Franz).
The fiancé of a fireman (DeLane Matthews) asks Lilly to help prove that a convicted felon, about to be paroled on an unrelated crime, is responsible for the murder of the fireman's first wife. The young mother was killed by a homemade bomb packed in a laundry-detergent box shortly before she was to testify in court against a man who exposed himself to her.
Lilly re-investigates the case of a murdered church organist (John Walcutt), when his Alzheimer's-stricken widow (Isabella Hofmann) begins having flashbacks of the night in question. Lilly's investigation has both Mitchell's son, Ryan (Jimmi Simpson), and daughter, Tina (Daisy McCrackin), demanding Lilly close the search.
After a drug addict (Dee Freeman) brings in an audio tape she found on which a fatal shooting is heard, Lilly reopens a 1973 murder case involving the death of a 21-year-old rookie cop (Cory Hardrict). The young officer was shot three times in the chest while responding to a call at a drug-infested housing project. Also on the tape are the victim's final words: "Runner! Runner! Runner!"
A petty crook, Ricky (Tim deZarn), hoping to get a reduced sentence, relates witnessing a young man washing blood out of his car the night a teen track runner was murdered. The young athlete, Paige Pratt (Summer Glau), was found shot, and her boyfriend Al Clarkson (Doug Kruse) was originally imprisoned for the crime.
Lilly investigates the case of Daniel Holtz, a college baseball player who was found beaten to death in an alley behind a gay bar in 1964. Daniel's mother comes to Lilly in the hopes that his killer can be brought to justice before she dies. Lilly discovers the maltreatment gay victims received in the 60's, when her investigation discloses that it may have been a policeman's nightstick that made the lethal blows.
When a young woman, Rosie (Laura Regan), wakes up from a coma, Lilly re-opens the fall in which her 6-year-old daughter Toya (Aynsley Lemon) died. Things get complicated when the mother remembers very little of that night, and Lilly feels especially motivated to find the killer, as Rosie was poor and living on welfare, reminding Lilly of her own past, and giving her an emotional bond to Rosie.
A college professor (Jeffrey Nordling), who lost everything − his career, his family, his reputation − after being suspected of murdering one of his female students (Kaitlin Doubleday) in 1995, offers new information regarding the case that he hopes will clear his name. He believes the student's death is connected to a copycat murder of a prostitute. Rush investigates the woman who was killed and the men in her life in order to discover which one of them killed her.
The 1958 death of an unknown 6-year-old boy found in a field inside a cardboard box is reinvestigated after a small suitcase with the child's picture and his old cowboy hat is left in front of a church. The new probe reveals that the rowdy boy lived at a Catholic-run orphanage and was adopted two days before his suspicious demise.
The shooting death of a man in his driveway is connected to the unsolved 1992 murder of a Democratic campaign worker whose lifeless body was thrown into a nearby river on election night. The investigation centers on the relationship the dead woman had with a present-day congressman. Apparently, the victim in the current homicide probed into the earlier slaying and discovered damning new evidence. Elsewhere, Lilly spies Kite flirting with a new ADA and gets jealous.
Lilly returns to her last case before joining the Cold Case Squad as she re-investigates the brutal triple homicide of a restaurant owner and his family, murdered in the restaurant bathroom in 2003. Also the other team member have personal reasons to closing the case; Jeffries grew up in the predominantly black neighborhood while Vera was the one assigned to the case when Det. Rush left.
Lilly and Valens reopen a presumed homicide from 1979 in which an unidentified victim's blood-drenched shoes, underwear and sheets were found in a trash bag, but no body. The investigation begins when a battered wife accuses her husband of murdering a girl in 1979 and brings in an amateur film from the time that supposedly shows him committing the crime.
When human remains are found outside a former state prison, the team re-opens the 1968 case of a dead inmate, murdered on the night Johnny Cash's Folsom Prison Concert was broadcast to prisons throughout the country. However, when it's revealed that the bones don't belong to the person everyone had assumed, the team must start the probe anew by first identifying who the victim was.
Det. Rush investigates the 1991 double murder of married illegal immigrants from Cambodia who were shot to death in their apartment and found by their 6-year old daughter. The now-teenage girl brings the case to Lilly after she discovers a bracelet once owned by her mother is for sale on the internet. The probe reveals that the parents had dark secrets unknown to their daughter.
Lilly reopens a 1990 murder case, in which a prep-school girl was found dead in a local swimming hole, after a present-day victim with similar markings is discovered at the same place. The investigation reveals that the victim of the earlier crime was routinely tormented by a trio of classmates who invited her to a sleepover the night she was killed.
An HIV-positive gay man asks Rush and Valens to re-investigate the case of his dead partner who died of strangulation in 1983. Not only was the victim outspoken in his views about AIDS education within the 1980's secretive gay community, he was also the member of a very prominent family, disowned by his father for his sexual orientation.
The 1953 murder of a white school teacher, a communist sympathizer who was involved in civil-rights issues, is reopened after the victim's youngest son asks for it to be reinvestigated. The probe reveals that the slain man was killed on the same day that the Rosenbergs were executed and was set to testify the next day before the House Committee on Un-American Activities.
The team re-opens the 2000 case of a prominent Puerto Rican assistant district attorney when rumors about his connection to a large amount of money gone missing at the time of his death start to circulate. However, his widow insists that the claims are not true. The re-investigation reveals that the victim was prosecuting a murder trial and the man convicted for the crime after his death may possibly be innocent.
A serial killer is to be released from a New Jersey prison based on a plea bargain made twenty-five years ago. Philadelphia homicide is asked to locate a potential crime committed while the killer was living in Philadelphia during the summer of 1977. A doorman was found strangled to death in a subway station in full uniform. The plot follows an evening at "The Rocky Horror Picture Show" involving the doorman, his girlfriend and the future serial killer. Valens received word from NYPD that his girlfriend was involved with credit card fraud and there's a warrant out for her arrest.
The discovery of nine human skulls leads Rush (Kathryn Morris) back to George Marks, the serial killer she was unable to incriminate months earlier, and who walked away a free man. As the detectives reinvestigate his mother's murder from 1972, George is forced to emerge from hiding to face Rush again. This time, their very lives are at stake in their final showdown.
When a note connected to a supposed suicide is found, the team re-opens the 1994 case of a high-school kid who fell from the roof of the school building after having served detention. In 1994 the death was deemed a suicide, but the newly-found note indicates that the victim might have been fearing for his life.
When the victim's credit card is suddenly used a year after his death, Lilly re-opens the 2005 case of a counselor at a teens' rehab center who was shot to death just two weeks before he was scheduled to testify in a murder case. During the probe, Lilly feels a strange connection to the victim, and her personal attachment may end up jeopardizing the case.
The team receives new evidence in a 1964 case which was then though to have been a hit-and-run. Now, a threatening letter addressed to the victim prompts Will and Kat to travel to Mississippi to re-investigate the death of a woman who was secretly involved in giving school supplies for black children.
When Dexter Collins, a young activist with a bright political future was found shot to death in 2005, it went down as a drug buy gone awry. Following a new tip regarding the location of the weapon, the police reopen the case and interview everyone from members of street gangs to his opponent for the city councilman seat.