Detective Lilly Rush from Philadelphia Homicide force is transferred to the Cold Case Unit. She kicks off her career as a Cold Case detective by reopening the 1976 murder of Jill Shelby, a 15-year-old girl who was found beaten to death at a party hosted by her wealthy neighbors, one of them being her boyfriend, after one of the neighbors' former housekeepers comes forward, claiming to have witnessed the murder. Lily must battle both the rich society and people reluctant to go back to that fateful night to solve the case.

The team reinvestigates the 1983 murder of 25-year-old Dana Deamer, a young wife and mother who was killed in an explosion outside her own house while picking up what was supposed to be a box of laundry detergent shortly before she was to testify in court against a man who indecently exposed himself to her in public. The daughter believes the man is culpable, but when the team delves into Dana's personal life, they discover a shocking secret that could lead them to the true killer.

When a serial rapist sends an intimidating letter to the Cold Case squad announcing his return to Philadelphia after five years of absence, the team reinvestigates the 1998 murder of Gail Chimayo, a 21-year-old college student who was believed to be one of his victims, in an effort to identify him before he strikes again.

The team reinvestigates the 1990 murder of 49-year-old Mitchell Bayes, a church organist, when his Alzheimer's-stricken widow begins having flashbacks from the night he died. The team soon learns dark secrets about the family that could lead them to the killer.

When a drug addict brings in an audio tape capturing the recording of a fatal shooting, the team reopens the 1973 murder of a young police officer, 21-year-old Joe Washington, who was killed after responding to a call at a drug-infested housing project. Rush soon discovers several inconsistences with the statement and fears a dirty cop may have been involved.

The team reopens the 1981 murder of Paige Pratt, a 16-year-old high school track runner, after a petty crook, hoping to receive a reduced sentence, comes forward claiming to have evidence that her boyfriend, then 21-year-old Al Clarkson was wrongly convicted of her murder. Rush and her new partner, Scotty Valens, get off to a rocky start.

A woman asks Lilly to reinvestigate the unsolved murder of her son Daniel Holtz, a 21-year-old former college baseball player, who was beaten to death outside of a gay bar in 1964 after it was discovered that he was homosexual. Things get personal however, when the team discovers a police nightstick at the crime scene, implying that a policeman may have been involved.

• Songs features in the intro: "The Shoop Shoop Song (It's in His Kiss)", by Betty Everett / "Remember (Walkin' in the Sand)", by The Shangri-Las.
• Song featured in the finale: "Turn! Turn! Turn!", by The Byrds.
• Brandon Routh has a guest role as young Hank.

The team reinvestigates the 2001 death of 6-year-old Toya Miles, who died after falling through her bedroom window, along with her then 23-year-old mother, Rosie, who survived, but suffered severe head trauma, putting her in a two-year coma. Her recent awakening makes Lilly and the squad try to put the pieces together to determine if this young mother or someone else is responsible for the tragedy.

When Lilly receives an anonymous phone call from a man who claims to have killed an elderly woman in 1989, the team investigates the disappearance of Krystal Hogan, an 81-year-old grandmother who went missing that same year. The team discovers that Krystal lived with her orphaned step-grandson, then 19-year-old James Hogan, whose lifestyle she disliked.

The team reopens the 1997 murder of Matthew Mills, a 20-year-old hitchhiker killed on his way back to Philadelphia after winning big in Atlantic City, when new evidence is uncovered linking a current case to his murder. Scotty learns a lesson in humility after he makes a poor call that hinders the investigation, and the team makes a stunning discovery that could also close the case.

The team reopens the 1995 murder of 21-year-old Holly Richardson at the request of one of her college professors, whose career ended in disgrace after he was suspected of her death after their affair was discovered. The professor hopes to clear his name after another young woman is killed in an identical fashion as Holly, though the team is skeptical about his innocence.

Lt. Stillman asks Lilly to reinvestigate one of his first cases as a homicide detective: the 1980 murder of 8-year-old Timothy Barnes, who was knocked out and left on the snowy ground and died tragically of hypothermia. Suspects include his own parents, a group of troubled teenage boys, and his priest.

After a young woman comes forward with new information about the death of her grandmother, Lilly and the squad reopen the unsolved 1939 rape and murder of a 25-year-old black woman, Sadie Douglas. During their investigation, the team uncovers racial tensions and a secret romance that could help identify the killer.

The team reopens the case of the 1958 murder of an unidentified 6-year-old boy, whose body was found in a cardboard box in a field outside Philadelphia, after a suitcase is found containing a photo of the boy, among other things. The team discovers that the boy may have been part of the government's radiation experiments on orphans.

Human remains found during a building demolition prompt the team to investigate the unsolved 1969 double murders of 22-year-old Julia Hoffman and 23-year-old Gerald Gary, two hippies who belonged to a group that facilitated access of illegal abortions.

After a high school basketball phenom receives threatening phone calls, the team reopens the 1987 murder of his father, 17-year-old Herman Lester, another star basketball player who was found stabbed to death hours after leading his team to victory in the State Championship. The team tries to determine if there is a link between the phone calls and the murder.

The team reinvestigates the 2000 murder of 39-year-old Greg Cardiff, a husband and father who was killed in a hit-and-run accident just a few minutes into New Year's Day, after a recovering alcoholic comes forward as the possible culprit. During the investigation, however, the team finds evidence that the victim was poisoned and already dead when the car hit him.

Suspicious evidence found at the scene of a current murder prompts the team to reopen the 1992 murder of 20-year-old Vanessa Prosser, a young and highly politically involved woman who was killed on the night of the 1992 presidential election. The team learns that the victim was dating a congressman with a dark secret.

The team reopens the 1985 murder of Charles Danville, a wealthy stockbroker who was shot and killed during an apparent carjacking gone wrong, after new evidence points towards premeditated murder. The team uncovers evidence that the victim may have been cheating his clients and having illicit relationships with his protégés.

When a juvenile delinquent comes forward claiming to have witnessed his mother's death, the team reinvestigates the 1989 murder of the young mother, 30-year-old Rebecca Morgan. The team soon discovers that the victim is not who they thought she was.

The team reopens the 1999 murder of Nash Cavanaugh, a 35-year-old military academy's strict swim coach who drowned in the academy pool, after the homicide division receives a note suggesting his death was a homicide. The team learns that the victim was a pedophile who preyed upon his weaker students.

When DNA evidence reveals a man was wrongfully convicted of murder, the team reopens the 1986 murder of Eve Kendell, a 15-year-old girl who was raped and killed during a date with her boyfriend, 16-year-old Mark Adams, who was also assaulted but survived, at a popular lover's lane. The team soon discovers the victim was a regular object of relentless attention, leading them to believe that her murder may have been a crime of passion.