A number of other well known actors and actresses appeared in F.I.S.T. They included Kevin Conway, Brian Dennehy, Rod Steiger, Melinda Dillon, Richard Herd, Peter Boyle and Red Hot Chili Peppers lead singer Anthony Kiedis.
Johnny and Abe spend the next couple of days in bars, when they are approached by Mike Monahan, who witnessed Kovak lead their labor riot. Mike offers Kovak and Abe positions in the Federation of Interstate Truckers (F.I.S.T.). They will only be paid based on how many members they can get and they at the time, reluctantly join. Kovak was given a car straight up to help to convince him to join. Johnny drives around trying to get the attention of a woman he met at a party a while back, Anna Zarinkas. After a few attempts, Johnny finally gets a date with Anna and they start seeing each other. During this time, Johnny is also starting to get a few members and this comes to the attention of the leaders of the people running the labor businesses. They feel a bit threatened by Kovak and try to offer him a deal to join them and be a voice in helping bring more labor workers. Kovak immediately rejects the offer, which results into him being set up and beat up. Kovak remains strong and holds his ground, as they get more people to join. We are then introduced to another leader of F.I.S.T., Max Graham. He is known by many labor workers and is a bit of a hot head. He doesn't respect Kovak or believe he should really represent F.I.S.T. This sets up something later in the film because Kovak doesn't forget about the hostility Max showed in the beginning.
Soon Mike, Johnny, and Abe begin working to get the F.I.S.T. members working at Consolidated Trucking a labor agreement. Management refuses to deal with them, resulting in the F.I.S.T. workers striking. The F.I.S.T. members set up a camp outside of Consolidated Trucking's gates. This only works for while, until the members of F.I.S.T. are pushed off the ground by physical force. This disgusts Mike, who goes into a truck and with intention to ram their gates. Instead Mike is shot at and killed. At Mike's funeral Johnny decides to get some real muscle to get his point across and accepts help from local gangster Vince Doyle. At a union meeting, Johnny tells Graham to leave, that the F.I.S.T. local would take care of things themselves. Vince's men attack trucks that are trying to make deliveries. Local mobsters and the members of F.I.S.T. join forces to storm the gates of Consolidated Trucking. In the end the President of Consolidated Trucking is forced to sign a labor agreement.
After the strike, Johnny and Abe travel throughout the Midwest, recruiting more workers to join F.I.S.T. as the union becomes stronger. Kovak becomes wealthier and marries Anna. Then a new crime figure Babe Milano comes on the scene - wanting in on what Johnny and Abe are doing. Kovac meets Milano with Doyle and although reluctant to involve him in his business, he decides it will be best for now.
The film then goes to 20 years after all the other events have taken place. F.I.S.T. is now a large union and is an important union for the workers. Johnny goes and has a meeting with Max and he informs him he will no longer be president of F.I.S.T., telling him that he should have never treated him the way he did. Johnny is now the president of F.I.S.T., but now he has Senator Madison after him as he suspects Kovak of having ties to the mafia. Later on Abe comes and visits Johnny and their relationship as friends have seemingly deteriorated as the years have gone by. Abe asks Johnny to cut off Milano and make the union clean again. Kovak ignores his request. Then Vince tells Johnny that Abe will testify against him and Milano and everybody else. Johnny says that he doesn't want Abe to be touched. Johnny is then called in to testify in front of the Senator, where he informs him that Abe has been killed and he believes that Kovak is responsible for it (although it was really Milano's men who did it). This shocks Johnny and as the Senator continues to accuse him of other crimes, Johnny erupts into an emotional outburst and storms out of the hearing. At night Johnny returns home and finds out that Anna and his children are missing. He runs throughout the house looking for them and gets his gun, but as he goes towards the staircase, is shot and killed by Milano's men. They feared that Kovak would cut Milano's mob off and testify against Milano. The movie ends with a bumper sticker on a truck saying, "Where's Johnny?"
Some locations used in filming included St. Raphael's Cathedral, Sacred Heart Church, the Fourth Street Elevator, E.J. Voggenthaler Co. and Dubuque Star Brewery. Filming was also done at the former Caradco manufacturing company in Dubuque. Portions of the Caradco building were fitted with new windows which were then purposely smashed for filming. The windows were replaced by the end of filming. Other Dubuque locations that were also visible in the finished film were the Dubuque County Courthouse and Saint Mary's Catholic Church.
Some filming was also done in the English city of Sheffield.
Despite the popular cast and strong reviews, F.I.S.T. was not a box office success. The minimal marketing and advertising the film received ultimately caused it to suffer financially.