Journalist Hunter S. Thompson and his attorney Carl Lazlo embark on a series of misadventures that blur the lines between sanity and chaos. Set against the backdrop of the 1960s and 1970s, the story kicks off with Thompson covering high-profile events, from drug trials to political campaigns, highlighting his eccentricity and unconventional reporting style. Lazlo, often pushing legal and moral boundaries, accompanies Thompson, driving him deeper into his own brand of gonzo journalism. The narrative underscores their tumultuous friendship, fueled by substance abuse and a disdain for societal norms, as they navigate through various wild situations meant to capture the zeitgeist of the era.

Despite their shared convictions and mutual understanding, conflicts arise as their paths diverge due to differing priorities and escalating complications in their professional and personal lives. Thompson's career hangs in the balance as his erratic behavior becomes more pronounced, while Lazlo pursues radical activism with increasing fervor. The progression of Thompson's assignments takes them to diverse settings, each punctuated with surreal and often absurd encounters that test their bond and sanity. The storyline weaves through these episodic vignettes, portraying a vivid tableau of countercultural America before reaching its inevitable conclusion.