The show was set and filmed in New York City, and with an ensemble cast of characters the storylines centred on the lives of police officers of the New York City Police Department (NYPD) and the firefighters and paramedics of the New York City Fire Department (FDNY), all working the same fictional district during the 3pm to 11pm - the 'Third Watch'.

After the September 11 terrorist attacks hit New York in 2001, series 3 opened with the award winning October 15, 2001 episode "In Their Own Words", featuring interviews with real-life NYPD and FDNY members who responded to the attacks. The following episode was titled "September Tenth".

In the series finale, "Goodbye to Camelot", broadcast on May 6, 2005, the third watch is disbanded after a grenade attack burnt down the police station.

The series followed the exploits of a group of police officers, firefighters, and paramedics in the fictional 55th Precinct and Fire Station 55 whose shifts fell between 3 p.m. and 11 p.m, the "third watch." The precinct and fire station were located on the corner of King Blvd and Arthur St.; hence the nickname "Camelot." Exterior shots of the 55th Precinct and the Firehouse were filmed in Long Island City, Queens. Third Watch succeeded in presenting all three branches of New York City's emergency services in the same show, reviving a failed attempt to do so nine years prior with the similarly-themed H.E.L.P. running for only one season in 1990.

The show balanced numerous single-episode events with other, ongoing storylines, some of which spanned multiple seasons. While Third Watch was lauded for its emotional and honest portrayal of the events surrounding the 9/11 terrorist attacks, it was also criticized in some circles for extremely detailed violence and prevalent (by network television standards) profane language. The show was created, produced, and written by John Wells and Edward Allen Bernero. The theme song for the show was "Keep Hope Alive" by The Crystal Method, except for the pilot episode when "Right Here Right Now" by Fatboy Slim was played during the opening sequence.

Third Watch was not renewed by NBC in the spring of 2005, making the sixth season the show's last. The series' finale, "Goodbye to Camelot," was aired in the United States on Friday, May 6, 2005. It was listed in the Bergen Record, the New York Times and other newspapers as a TV show that was canceled too early.

Co-creator John Wells had wanted to do a show about paramedics for some time before Third Watch began, but did not think he had enough material to make such a show. Ed Bernero, a former Chicago cop, had wanted to do a police drama partly based on his own experiences. The two worked together on the short lived show Trinity, and after cancellation Wells asked Bernero if he wanted to co-create a show with him. Third Watch was a combination of Wells' paramedics show and Bernero's police show.

Originally the show was only going to be about the police and paramedics, but firefighter Jimmy Doherty was added to the show after actor Eddie Cibrian auditioned for the role of police officer Maurice 'Bosco' Boscorelli. Cibrian lost out to Jason Wiles, but impressed the producers so much that they decided to put him in the show as a new character. Bernero said, "Well, we don't have any firefighters", and the fire aspect of the show was added in to produce a show revolving around all 3 emergency services.

The series consists of six seasons with a total of 132 episodes produced and broadcast from September 23, 1999 to May 6, 2005.

Third Watch's original ensemble cast in the series' first season consisted of Michael Beach, Coby Bell, Bobby Cannavale, Eddie Cibrian, Molly Price, Kim Raver, Anthony Ruivivar, Skipp Sudduth, and Jason Wiles.