In December 1970 in Marseilles, France, a plainclothes policeman is observing former longshoreman turned entrepreneur Alain Chanier (Fernando Rey) chatting with some unsavory types. Chanier is being tailed by the undercover cop because he is a kingpin in smuggling heroin overseas - a fact that costs the cop his life when he later returns home and is shot in the face by Pierre Nicoli (Marcel Bozzuffi), Chanier's henchman.
Meanwhile, in Brooklyn, NY, a corner Santa is chatting with some children outside a seedy bar while a hotdog vendor completes a transaction. The Santa is Detective Jimmy "Popeye" Doyle (Gene Hackman) and the vendor is his partner, Detective Salvatore "Buddy" Russo (Roy Scheider), whom Doyle nicknames "Cloudy." The two narcotics cops are staking out the bar in hope of finding a pusher named Willie Craven (Alan Weeks). Cloudy enters the bar and begins frisking suspects. Craven sees the commotion and suddenly flees outside, with Popeye and Cloudy in hot pursuit. The cops chase him on foot to a deserted lot where he falls and is beaten by both cops before Russo implores Doyle to stop. Once the two cops calm down they confusingly interrogate Craven, trying to get information on his drugs connection.
In France, Alain Chanier finishes a day overseeing dock work and drives home to his seaside villa and his young trophy wife (Ann Rebbot), who clearly has expensive tastes. The two exchange gifts for their pending trip to the US. Chanier later meets his gunman Nicoli at a rendezvous point for a friend of Chanier, TV personality Henri Devereaux (Frédéric de Pasquale). Devereaux is traveling to the US to make a film and has decided to aid Chanier's smuggling effort because he needs money. Nicoli believes involving Devereaux is a mistake but is reassured by Chanier.
In NYC, Popeye and Cloudy sign off for the night and Popeye takes his reluctant partner to The Shea, a big nightclub. Popeye notices one table in particular, populated by known narcotics connections who are being entertained by a free-spending grease-haired type with a buxom blonde as his companion. Popeye smells a scam and persuades Cloudy to help him tail the greaser and his blonde babe. Throughout the night they tail the two, watching them drop off a suitcase in Little Italy and then switch cars early the next morning from an attractive coupe to a beat-up sedan. They then drive to a candy store/luncheonette, "Sal and Angie's", in a working-class area of Brooklyn. Peering inside as the couple prepares to open for the day, Popeye and Cloudy notice that the blonde is now a brunette, having worn a wig the night before.
The two cops realize they are on to something and for the next week they stake out the candy store. Combing records they find that the greaser is Salvatore "Sal" Boca (Tony Lo Bianco) and his wife is Angie (Arlene Farber). The candy store's income could not explain Sal's free-spending ways. The posh coupe is owned by Angie while the beat-up sedan is owned by Sal's brother Lou (Benny Marino), a garbageman in training, and all three Bocas have criminal records. The candy store is regularly visited by unsavory types from New Jersey, and Sal makes numerous trips to an expensive condo in Manhattan at which lives lawyer Joel Weinstock (Harold Gary), a known connection who bankrolled a heroin shipment from Mexico.
Popeye and Cloudy raid a junk-house bar; one afro-headed type (Al Fann) talks back at Popeye and is hauled into a men's room to be beaten up - actually cover so Popeye can debrief his informant, who reveals that a big shipment is due within a few weeks that will satisfy everyone in the city. In order to make the ruse look convincing, Popeye punches his buddy in the jaw, a bit too enthusiastically.
Popeye's boss, Walt Simonson (Eddie Egan, the real-life inspiration for Popeye Doyle), is reluctant to let the two cops continue with their investigation of Boca, pointedly reminding Popeye of a previous case where his hunches backfired. But with Joel Weinstock, whom the police have long wanted to arrest, potentially involved, Simonson relents and goes to court for a wiretap on Boca's house and candy store. The federal Bureau of Narcotics and Dangerous Drugs (BNDD) now becomes involved and assigns Agents Bill Mulderig (Bill Hickman) and Bill Klein (Sonny Grosso, the real-life inspiration for Cloudy Russo), who've worked with Popeye before; Popeye and Mulderig are at constant loggerheads because Mulderig blames Popeye for the death of a policeman in a previous case and doesn't believe Popeye's hunches to begin with.
Chanier, Nicoli, and Devereaux arrive in NYC and Devereaux brings with him Chanier's Lincoln, signed for in Chanier's stead. They speak fair English, but nonetheless have an interpreter, La Valle (Andre Ernotte), with them. La Valle escorts Chanier to a police auction of impounded cars and identifies Lou Boca as the scrap metal buyer for Chanier's business (suggesting how the Bocas may have linked up with Chanier).
After several days of monitoring mundane conversations, the wiretap finally brings Popeye and Cloudy their first break - Chanier phones Sal to arrange a 12 o'clock meeting the next day. Popeye, Cloudy, and Mulderig tail Sal to midtown Manhattan, where they spot Sal meeting with Chanier and Nicoli. While Mulderig follows Sal, Popeye and Cloudy tail Chanier, dubbed "Frog One," and Nicoli as they walk through the city. The Frenchmen stop to eat at an expensive restaurant, which the cops observe while standing outside in freezing temperatures and eating cold pizza with lukewarm coffee. Later, Popeye finds out that Frog One is staying at the Westbury Hotel, but Mulderig still doesn't believe Popeye is on to anything, leading to a brief argument.
At Joel Weinstock's condo, Howard (Pat McDermott), a chemist, tests a sample of Chanier's heroin and it measures to 89% pure. There are sixty kilos due to arrive and when all is said and done it will total out to $32 million with a half-million cash down payment. Weinstock, however, wants to wait before the switch is made, much to Sal's displeasure as Sal fears that Chanier will abort the deal if Weinstock drags it out too long.
The next day Popeye sees Chanier leave the hotel without a tail (Mulderig is distracted with a phone call). He tails Chanier himself, almost loses him at a flower shop, but then picks him up again at the Grand Central subway station. They play a cat-and-mouse game on the platform, but the wily Chanier manages to hop back on a train at the last moment and waves goodbye as the furious Popeye futilely runs after the train.
Chanier meets Sal in Washington DC - Sal followed there by Klein - where Chanier insists that the deal must be consummated by the end of the week, despite Sal's protests that his mob pals want to wait. On the flight back to New York, Chanier expresses his worries to Nicoli, who points out that Sal's concern about the police is warranted. The Frenchmen agree that Doyle is the main problem, and Nicoli volunteers to assassinate Doyle. Chanier reluctantly agrees, unaware that a fight has erupted between Popeye and Mulderig, and that Popeye has been taken off the case by a furious Simonson.
The dejected Popeye returns to his Brooklyn apartment building, where he is fired upon by Nicoli from the roof. Popeye manages to enter the building and pursues Nicoli to the roof, and then back down when he sees Nicoli fleeing. Nicoli runs to a nearby elevated train station and boards the train while Popeye screams for a uniformed conductor on board to stop him. As the train proceeds, the conductor follows Nicoli as he moves forward through the train. Popeye commandeers a Pontiac Le Mans from a flabbergasted citizen. Nicoli kills the uniformed conductor and seizes the motorman, forcing him to keep the train going. Popeye furiously pursues in the car, barely escaping as other cars sideswipe him. He nearly strikes a woman pushing her child in a baby carriage. Nicoli then kills a passenger who tries to intervene, and the terrified motorman collapses with a heart attack, locking the train on a collision course with a stopped train. The two trains crash and passengers, including Nicoli, are thrown about. Despite injuries and losing his gun, Nicoli slips out undetected - by everyone except Popeye. Nicoli starts down the stairs but is cornered by Popeye, and when he tries to flee he is shot dead.
Popeye and Cloudy, apparently now back on the case, tail Sal as he takes the Lincoln to a side street. The police stake out the car all night until a gang of thieves tries to strip it, but they are arrested by a horde of policemen and the car is towed to a garage to be searched as evidence. The mechanic (Irving Abrahams), cannot find any narcotics in the car, but Popeye refuses to believe it. While Devereaux (who signed for the car) and La Valle argue with the garage desk sergeant, Cloudy notices a 120-pound discrepancy between the car's listed weight and actual weight. The mechanic reveals one area he didn't open up - the car's rocker panels underneath the doors. Popeye chews him out and then helps open up these panels, and the stash is found. The car is repaired, the stash replaced, and it is all returned to Devereaux, while the police now wait.
Devereaux meets again with Chanier and is reluctant to do any more favors, until Chanier reveals that Devereaux is now an accomplice - to Devereaux's surprise and horror. Devereaux reluctantly allows Chanier to drive the car to an abandoned factory outside the downtown area. There the heroin stash is revealed and tested positively. The stash is hidden inside the building and cash payment is hidden in the rocker panels of the junker car Lou Boca bought. With the deal consummated, the Bocas briefly celebrate and Sal drives Chanier toward the city - and right into a police roadblock led by Popeye. Sal drives back to the factory with police in pursuit, and the mobsters hide inside the main building while Chanier hides in a secondary building. A gunfight ensues, in which Sal Boca is shot dead. Popeye hunts for Chanier inside the dripping, junk-filled warehouse. Popeye hears a noise and fires his gun, but it turns out to be Agent Mulderig, whom Popeye has killed. Determined to get Frog One at any cost, Popeye strides down a corridor to where he believes the Frenchman is hiding. We hear a single gunshot. An epilogue informs us that Chanier escaped and is believed to be living in France, and that Doyle and Russo were suspended from narcotics duty.
