Med tihotapljenjem mamil iz Turčije oblasti zasačijo Billyja in sodišče ga kot grešnega kozla obsodi na 30-letno zaporno kazen. Če naj sploh preživi, mu ostane le še beg oz. vožnja s "polnočnim ekspresom".Mladega Američana Billyja Hayesa (Brad Davis) turške oblasti aretirajo na letališču in izkaže se, da je skušal pretihotapiti hašiš. Obsodijo ga na kazen v krutem turškem zaporu, kjer so jetniki prepuščeni zakonu močnejšega. Tam spozna zahodnjaške sojetnike, med njimi Američana (Randy Quaid), Angleža (John Hurt) in Skandinavca (Norbert Weisser). Kot grešnega kozla ga v politično pristranskem procesu obsodijo na dolgotrajno zaporno kazen in če naj Billy sploh preživi v neusmiljenem okolju, mu ostane le še beg od tam oz. vožnja s "polnočnim ekspresom", kot temu rečejo v jetniškem žargonu. Briljantna igra, zanesljiva režija in sijajna glasbena podlaga prinašajo od prvega prizora do epiloga osupljivo filmsko izkušnjo. Oliver Stone si je prislužil oskarja za najboljši prirejeni scenarij, Giorgio Moroder pa za izvirno glasbo z naslovno skladbo, ki jo poje Chris Bennett.
On October 6, 1970 while boarding an international flight out of Istanbul Airport, American Billy Hayes is caught attempting to smuggle 2 kilos of hashish out of the country, the drugs strapped to his body. He is told that he will be released if he cooperates with the authorities in identifying the person who actually sold him the hash. Billy's troubles really begin when after that assistance, he makes a run for it and is recaptured. He is initially sentenced to just over four years for possession, with no time for the more harsh crime of smuggling. The prison environment is inhospitable in every sense, with a sadistic prison guard named Hamidou ruling the prison, he who relishes the mental and physical torture he inflicts on the prisoners for whatever reason. Told to trust no one, Billy does befriend a few of the other inmates, namely fellow American Jimmy Booth (in for stealing two candlesticks from a mosque), a Swede named Erich, and one of the senior prisoners having already served seven years, an Englishman named Max, the latter two also in for hash related charges. One prisoner not befriended is Rifki, who wields power in the prison as the unofficial eyes and ears for the guards. As Billy, his family and his girlfriend Susan attempt through legal and diplomatic channels for Billy's release, Max tells him that the only way out is to "catch the midnight express" aka escape, which is what Jimmy is continually trying to do. When Billy's situation changes, he becomes more desperate in every sense of the word. It seems as if Billy has only two options: to let the prison ultimately figuratively then literally kill him, or to somehow regain control of his life through whatever means available.