The novel criticizes fanaticism, both as religious extremism and as a societal issue. When Tom first meets Jim Casy, the former preacher shares his realization that organized religion stifles life, particularly in terms of sexuality. He found a connection between the "Holy Spirit" and sexuality during his preaching days. Later, at the government camp, Rose of Sharon is frightened by a fanatical religious woman who warns her that dancing is sinful and predicts it will cause her to lose her baby. This fanatic also tells Ma that religion endorses an economic class system that perpetuates poverty. She quotes a preacher: “(A preacher) says they’s wicketness in that camp. He says, ‘The poor is tryin’ to be rich.’ He says, ‘They’s dancin’ an’ huggin’ when they should be wailin’ an’ moanin’ in sin.’” Such religious extremism is portrayed as a rejection of life and is linked to business in its economic deprivation and denial.

A crucial lesson from the Joads' journey, and that of their real-life American counterparts, is that social fanaticism and prejudice against the “Okies” exacerbated the crises of the 1930s in California. The fear of migrants, paired with a lack of faith in the government’s capability to handle temporary issues, often led to violence. This fear also resulted in dire consequences like starvation, malnutrition, and homelessness. Looking back, it's evident that World War II "resolved" the migrant problem by absorbing the workforce into the war effort. It would have been much better if California had developed emergency solutions during this period of major social change, which could have served as a historical precedent.