Dr. Joan Watson, a surgeon-turned-sober companion, is hired to help with the rehabilitation of Sherlock Holmes, an eccentric man who uses his observation skills to aid the New York Police Department. What starts as merely a job develops into a partnership between Joan and Sherlock.
Holmes and Watson continue to consult with the NYPD on mysterious cases, but the appearance of Holmes's brother Mycroft sends their lives spiraling into chaos.
As Watson settles into her own skin as an independent investigator, Holmes returns and brings with him a new partner, Kitty Winter, whom he has taken under his wing. Watson is drawn back to Holmes's world, as Kitty struggles to find a place for herself as the two fall into their old rhythm.
With Holmes barely hanging on as he and Watson lose their jobs with the NYPD and he struggles with his addiction, he has to contend with his father's arrival and the vicious cycle he always thrusts him into.
Holmes and Watson continue helping Captain Gregson solve mysterious cases, which brings a face from Holmes's past back into their lives as government conspiracies and gang wars dominate their reality.
Holmes struggles with a medical diagnosis that puts both his career and sobriety on the line. Watson's personal relationships are shaken up in the wake of two unexpected deaths, leading to a life-changing personal decision.
Holmes and Watson embark on a new journey as consultants for Scotland Yard. But as tragedy hits close to home, they have to reckon with Holmes's legal troubles in the US, which jeopardizes their chances of going home.