Sherlock is reunited with “M.” a British criminal who appears to have followed Sherlock to New York. Meanwhile, Joan has reservations about leaving Sherlock and taking on a new client.

Sherlock pursues Martin Ennis, an unpredictable criminal, before he strikes again. During the investigation, Sherlock is forced to work alongside Kathryn Drummond, the FBI profiler who literally wrote the book on Ennis. Meanwhile, Watson faces eviction from her apartment.

As Sherlock reels at the reappearance of his former lover, Irene Adler, a series of flashbacks unravel the tumultuous events that led to his downfall into addiction. Meanwhile, he and Joan once again find themselves in the crosshairs of the enigmatic Moriarty.

Sherlock is called to London to revisit an old case, where he is forced to face his older brother, Mycroft. Although the siblings suffered a drastic falling-out a few years earlier, Mycroft allows Sherlock and Joan to stay in his new home, 221B Baker Street. With Joan in the middle, the brothers are forced to confront their very complicated history.

When a beautiful young woman is murdered, Holmes and Watson investigate her ties to a billionaire CEO. Meanwhile, Mycroft makes a case for Sherlock to move back to London.

Rising tension between Sherlock and Joan brings their partnership to a crossroads, but they endeavor to put their differences aside while they help Sherlock's brother, Mycroft, who faces accusations of treason and murder.

Sherlock returns to New York with a new apprentice and a renewed interest in working with the NYPD after being fired by London’s MI6. However, Gregson won’t let him resume consulting for the department without permission from his former partner, Joan, the NYPD’s new go-to private investigator.

Holmes and Kitty investigate the murder of a postal store owner whose death is connected to the illegal diamond trade. Meanwhile, Gregson's career is placed in jeopardy when he hits a fellow NYPD officer.

While Kitty tries to find a runaway teen, Sherlock and Joan work a case in which the murder of a brilliant bioengineer looks to be at the hands of a drug cartel. Also, Joan makes a major life decision but worries it will impact Sherlock negatively, not knowing that Sherlock has big news of his own.

Holmes and Watson find themselves in the middle of a civil war being fought on the Internet when a member of Everyone, the anonymous hacker group they periodically work with, is murdered.

Holmes and Watson take on an investigation of a personal nature when Holmes’ recovery sponsor, Alfredo, suddenly disappears. As they delve into Alfredo’s life for clues, Holmes questions whether their friend has been abducted, or worse, if he suffered a relapse into addiction.

When Holmes faces criminal charges in the aftermath of his recent violent behavior and relapse, his powerful father arrives in New York to fix his estranged son’s legal difficulties by any means necessary. Also, with Holmes and Watson’s consultancy with the NYPD in jeopardy, Holmes concentrates on the case of a missing wife believed to have been killed by her husband to try and get back in the department’s good graces.

Captain Gregson’s colleague from Narcotics asks Holmes to orchestrate the perfect heist inside the heavily armed and virtually impenetrable compound of a drug-dealing biker gang. Also, when Watson assists Fiona Helbron, who helped her on a recent case, she makes a surprising discovery about Holmes.

When Watson runs into Captain Gregson and his secret girlfriend, a former NYPD officer, she inadvertently sets the couple’s breakup in motion. Also, Holmes and Watson investigate the murder of a wealthy woman who left her considerable estate solely to a beloved dog.

Holmes and Watson’s lives are threatened by an influential, worldwide criminal network connected to the murder attempt on Morland Holmes. Also, Sherlock’s grievances with his father threaten their alliance to bring their mutual adversary to justice.

Captain Gregson lobbies to include Holmes and Watson when his unit is selected to receive a city commendation for its exemplary work. Also, as Holmes and Watson consult on the investigation into a financial analyst’s murder, they are drawn into the world of asteroid research.

Holmes and Watson investigate the murder of a former professional eSports video game player who died after being assaulted in front of his fans during a live video stream. Also, Shinwell approaches Joan for advice when his teenage daughter asks to meet with him for the first time in years.

Season 5 ends with Holmes and Watson pursuing an elusive criminal as a gang war erupts in New York City. While the NYPD works to contain the violence, the two investigate the murder that appears to have ignited the city-wide conflict and discover that a familiar face is pulling the strings.

Holmes and Watson retrace Holmes' steps after Holmes finds himself in possession of a severed head and can't remember anything about the last six hours.