John Amsterdam (Nikolaj Coster-Waldau) is an NYPD homicide detective who is 400 years old, but has the appearance of a 35-year-old. He was a Dutch soldier in Manhattan in the year 1642 when he stepped in front of a sword to save the life of a Native American girl during a massacre of her tribe. The girl in turn rescued Amsterdam by weaving a spell that conferred immortality upon him. It was also prophesied that he would not age until he finds his one true love, and only then will he become whole and ready for mortality. Flashbacks in different episodes of the show reveal Amsterdam's centuries of life since, using many names, though usually retaining "John", marked by loss as his friends, lovers, children (63), and dogs gradually grow old and die. Amsterdam is a recovering alcoholic who regularly attends Alcoholics Anonymous meetings, having remained sober since 1965. In his lifetime he has joined the Army three times, in addition to the Coast Guard, Marines, and Navy. He stated that he never joined the Air Force because he "doesn't like heights". He has taught historyat a university, served as a physician during the American Civil War, was a furniture maker at the turn of the 20th century, a portrait painter just before the outbreak of World War I, and by 1941 an attorney. At some point he attended Columbia University and served in the CIA. (See below for a detailed timeline.)
Amsterdam's quest to find his "true love" drives the series. But in each episode as a policeman he has crimes to solve, which he does using his deep and often personal knowledge of history, depicted as flashbacks. Though estranged from and unknown to most of his many descendants, except his 65-year-old son Omar, he tries to keep track of them and aids them when possible.
The title sequence is a time lapse series of images of the place where Amsterdam received his "gift", from the forests and Native American camps of the 17th century which evolves into modern Times Square in the city of New York.