The song refers to both the riots at the 1968 Democratic National Convention in Chicago, as well as the trial of the Chicago Eight, where protesters at the convention were charged with intent to incite a riot. The first line of the song: "So your brother's bound and gagged, and they've chained him to a chair" refers to Bobby Seale, the defendant who was gagged and bound to a chair in the courtroom following repeated outbursts. On Four Way Street, Nash dedicates the song to "Mayor Daley".
The line "Won't you please come to Chicago just to sing" refers to Nash pleading with band mates Stephen Stills and Neil Young to come to Chicago to play a benefit for the Chicago 8 defense fund.
In August 2009, Pink Floyd's David Gilmour released an online version, titled "Chicago - Change the World", on which he sang and played guitar, bass and keyboards, to promote awareness of the plight of Gary McKinnon. It featured Chrissie Hynde and Bob Geldof, plus McKinnon himself, and was made with Nash's support.