Frank Serpico (Al Pacino) covered in blood and slumped in the backseat of a police car as it races to a hospital with lights and sirens blaring. He has just been shot in the face. The rest of the movie tells the story of Serpico's career up to this moment, starting with him becoming a police officer in 1960. He is very idealistic and believes in non-brutal methods to catch criminals. Serpico also refuses to join in on police corruption, specifically that which involves shaking down and taking payoffs from gambling and drug dealing organizations. His refusal to take bribes earns him the suspicion of his fellow officers throughout the majority of the precincts to which he is assigned. Additionally, Serpico finds trouble fitting in due to his embrace of the counterculture of the 1960s: He moves to Greenwich Village, grows his hair and beard long to the point where he must maintain a plainclothes appearance, and associates with a more left-wing crowd that is distrusting of the NYPD.
At first Serpico tries appealing to his bosses about the corruption, but gets nowhere. He enlists a highly-connected fellow officer, Bob Blair (Tony Roberts) in his fight against corruption, but not even he can crack the city administration's general indifference. His campaign and the resulting complications and harassment within the department take a toll on his mental health and his relationship with fiancee Laurie (Barbara Eda-Young), who ultimately leaves him. After meeting a sympathetic police inspector who agrees to assist him with both disrupting the gambling rackets and later calling attention to the problem by going to the New York Times, he is transferred to narcotics, as he has always wanted. However, he finds himself in an even more corrupt and hostile atmosphere than before, where he has mostly enemies and almost no allies due to the reputation he has garnered. As a result, he is shot in the face during a raid on a heroin lab due to his fellow officers' reluctance to come to his aid. After being left for dead and eventually discovered by two uniformed officers, the story takes over from the beginning and shows a recuperating Serpico being tended to by his family and few remaining friends as well as being anonymously harassed with hate mail.
At the end of the film, Serpico testifies to the Knapp Commission on police corruption. The film ends with him waiting to board a ship; despite being promoted to detective (a lifelong ambition of his) and being decorated by the department for "conspicuous bravery in action" (along with the two officers who abandoned him during the drug raid) he resigns from the NYPD and emigrates to Switzerland.