Charlotte is a sixteen-year-old British student at Sherringford Academy in Connecticut and the descendant of the famous detective Sherlock Holmes. She possesses a hyperactive, analytical mind and relies on sharp observational skills taught to her since childhood. Sent to the United States as a disciplinary measure by her family, she operates a makeshift chemistry lab on campus and maintains a guarded, eccentric demeanor.

James is a sixteen-year-old student at Sherringford Academy and the descendant of Dr. John Watson. Though he misses his former life in London, he attends the Connecticut prep school on an athletic scholarship. He harbors a deep fascination with his family's history and possesses a strong emotional intelligence that contrasts with Charlotte's purely analytical approach.

Detective Ben Shepard is the local law enforcement officer assigned to investigate crimes occurring at Sherringford Academy. He initially views Charlotte and James as primary suspects due to their proximity to the victims. He maintains a firm but somewhat sympathetic approach to questioning the teenagers.

Mr. Watson is James's father, currently living in Connecticut with his new wife and children. He has not spoken to his son in four years following a bitter divorce but attempts to bridge the gap now that James attends school nearby. He stays in touch with the Holmes family and maintains extensive files on their exploits.

Milo Holmes is Charlotte's older brother, who operates an international security service based in London. He treats his younger sister with a patronizing attitude, viewing her as someone who requires constant supervision. He commands vast resources and connections with foreign governments.

August Moriarty is a mathematical genius and a descendant of the notorious Professor Moriarty. He previously worked as a live-in tutor for a fourteen-year-old Charlotte in England. His tenure with the Holmes family ended in a disastrous scandal that severely impacted his academic career and personal life.

Lucien Moriarty is August's older brother and an active participant in his family's criminal operations. He harbors deep resentment toward the Holmes family following the events that ruined his brother's career.

Bryony Davis-Downs is engaged to August Moriarty and currently works as a nurse at the Sherringford Academy infirmary. She crosses paths with James when he seeks medical attention for a concussion sustained during rugby practice.

Lee Dobson is an athletic student and rugby player at Sherringford Academy. He targets female students on campus and initiates a violent fistfight with James after making crude remarks about Charlotte.

Elizabeth Hartwell is a freshman at Sherringford Academy who takes a romantic interest in James. She becomes inadvertently entangled in the dangerous events surrounding Charlotte and James on campus.

Lena is the daughter of an oil tycoon and Charlotte's roommate at Sherringford Academy. She embraces a party-girl lifestyle and willingly participates in Charlotte's various campus schemes.

Tom is James's roommate at Sherringford Academy, attending the prestigious school on a scholarship. He often feels outclassed by the immense wealth of his peers but attempts to fit in by dating Lena.

Mr. Wheatley is the creative writing instructor at Sherringford Academy. He takes a highly specific interest in the legendary detective families and frequently questions James about Charlotte's deductive methods.

Abbie is Mr. Watson's new wife, residing with him and their two young children near Sherringford Academy. She offers a comfortable, caring environment when James and Charlotte require a safe place to stay.

Leander Holmes is Charlotte's uncle and an old university friend of Mr. Watson. He coordinates with James's father to ensure the newest generation of their respective families cross paths at school.