Boss was developed by Farhad Safinia in late 2010, with creative input from Kelsey Grammer and his production company Grammnet Productions. In November 2010, the script was shopped around to various cable networks and following a heated and contentious bidding war, Starz placed an eight episode order for the series, based solely on the strength of the script. This was in keeping with Starz business model of not ordering pilots but rather green-lighting projects straight-to-series. Safinia wrote the pilot, Gus Van Sant was attached to the project as director, with Grammer, Safinia, Van Sant, Richard Levine, Lyn Greene, Brian Sher and Stella Bulochnikov-Stopler serving as executive producers.

Casting announcements began in November 2010, with Grammer first to be cast. He portrays Tom Kane, "the Mayor of Chicago who is diagnosed with a degenerative mental condition that only he and his doctor know about." Next to join the series was Connie Nielsen as Meredith Kane, Tom's wife, "Meredith and Kane have a bad marriage and barely speak when they aren't in public." Jeff Hephner was next to be cast as Ben Zajac, "the state's treasurer, an impeccably handsome and ambitious Chicago native who is clearly about to become a major player on the Chicago political scene." Hannah Ware and Kathleen Robertson were the last actors to join the main cast, with Ware playing Emma Kane, Tom Kane's estranged daughter, and Robertson playing Tom Kane's personal aide.

Starz later announced that Martin Donovan, Francis Guinan, Rotimi Akinosho, Karen Aldridge, Troy Garrity, Ricardo Gutierrez, James Vincent Meredith and Joe Minoso had joined the series as recurring guest stars. Martin Donovan was cast as Ezra Stone, "A savvy Yale graduate, and senior advisor to Kane, Stone knows the Mayor better than anyone. Whether it’s pushing Kane’s agenda, or assisting with personal matters, Ezra always delivers." Francis Guinan was cast as Governor McCall Cullen, "The governor of Illinois, Cullen hates playing along the with the Mayor’s apparent unwavering support for his re-election bid. And his ugly temper is getting even worse." Rotimi Akinosho was cast as Darius, "a muscular drug dealer who’s covered in tattoos, but he’s smart, well spoken, and cares for his sick uncle." Karen Aldrige was cast as Dr Ella Harris, Mayor Kane's neurologist and the only other person who knows about his current medical condition. Troy Garrity was cast as Sam Miller, "a politically savvy journalist for The Sentinel, with a nose for a real story." Ricardo Gutierrez was cast as Alderman Mata, "Political boss of the 30th ward, Mata is a thug in a suit who believes the ends justify the means, however vicious." James Vincent Meredith was cast as Alderman Ross, "Kane’s biggest rival", and Joe Minoso was cast as Moco Ruiz, "A construction worker, Ruiz is one of Mata’s guys."

Filming of the series took place between April 27, 2011, and July, 27, 2011, on location in Chicago, Illinois.

At the 2011 Television Critics Association Summer Press Tour, Starz announced that Boss would premiere on October 21, 2011. The series is produced by Category 5 Entertainment, Grammnet Productions and Lionsgate Television.