- Arsène Lupin III: Yasuo Yamada
- Lady Clarisse d'Cagliostro: Sumi Shimamoto
- Daisuke Jigen: Kiyoshi Kobayashi
- Fujiko Mine: Eiko Masuyama
- Goemon Ishikawa XIII: Makio Inoue
- Inspector Koichi Zenigata: Gorō Naya
- Count Cagliostro: Tarō Ishida
- Groundskeeper: Kōhei Miyauchi
- Jodo: Ichirō Nagai
- Gustav: Tadamichi Tsuneizumi
- Waitress: Yoko Yamaoka
In Monaco, gentleman thief Arsène Lupin III and Daisuke Jigen rob a casino and flee in a Fiat 500, only to discover that their entire haul is counterfeit. Lupin recognizes the distinctively high quality counterfeit bills from his early days as a thief when he was almost killed while searching for their source. He decides to seek out the source again, and the two head off to the rumored source of the bills, the Grand Duchy of Cagliostro. Shortly after arriving, they rescue a young girl being pursued by a gang of thugs, with her and Lupin falling off a cliff while escaping. Lupin is knocked unconscious, and the girl captured, but she leaves him a distinctive signet ring. Lupin later discovers that the girl, Clarisse, is the princess of Cagliostro and is to be married to the Count, the country's regent. The Count wants to cement his power and recover the fabled ancient treasure of Cagliostro, for which he needs both his ancestral ring and the princess's. After narrowly escaping a group of the Count's elite assassins, Lupin calls on Goemon Ishikawa XIII to help him and Jigen in their new quest to rescue the princess. He also tips off his longtime pursuer, Inspector Koichi Zenigata, to his whereabouts to provide a distraction. Zenigata's presence and a party give Lupin enough cover to sneak into the castle. There he finds his former lover, Fujiko Mine, posing as Clarisse's lady-in-waiting and she tells him where the princess is being held. Lupin makes his way to Clarisse, returns her ring, and promises to help her to escape. Before he can act, the Count ambushes them with his assassins and Lupin is dropped down a trapdoor into the bowels of the castle. The returned ring turns out to be a fake, left by Lupin as a practical joke as part of his plan to be delivered into the area he wants to investigate. Infuriated, the Count flushes him deeper into the cellars, which are full of the bodies of spies killed while trying to learn the secrets of Cagliostro and the counterfeit bills. While down there, Lupin bumps into Zenigata, who was accidentally dropped down earlier. The two form a pact to help each other escape, which they accomplish by overpowering the assassins sent to recover the ring. Their escape leads them to a room full of printing presses—the source of the counterfeits. Zenigata wants to collect evidence, but Lupin points out they must escape the castle first. They start a fire as a distraction and steal the Count's autogyro. However, as they attempt to rescue Clarisse, Lupin is shot. Clarisse offers the ring to the Count in exchange for Lupin's life. After securing the ring, the Count's attempt at betrayal is foiled when Fujiko's quick actions allow her, Lupin, and Zenigata to flee. While Lupin is convalescing, Zenigata tries to convince his superiors at Interpol to prosecute the Count for counterfeiting, but fearing political repercussions, they halt the investigation and remove him from the case. Meanwhile, despite his wounds, Lupin vows to stop the wedding and rescue the princess. Fujiko tips off Lupin on a way to sneak into the castle, and makes a plan with Zenigata to publicly reveal the counterfeiting operation under cover of pursuing Lupin. The wedding appears to go as planned with a drugged Clarisse until Lupin's "ghost" disrupts the ceremony. The Count calls his guards, but Lupin makes off with Clarisse and both her and the Count's rings. Meanwhile, Zenigata and his squadron arrive in the chaos and the detective leads Fujiko, posing as a television reporter, to the Count's counterfeiting facility to expose the operation to the world. Lupin and Clarisse flee the Count, the chase ending on the face of the castle's clock tower. Lupin is forced to surrender the rings to save Clarisse, and they are both knocked into the lake surrounding the tower. The Count uses the rings to reveal the secret of Cagliostro, but is crushed to death by the mechanism as it moves to unveil the treasure. Lupin and Clarisse watch as the lake around the castle drains to reveal exquisite ancient Roman ruins—the true treasure of Cagliostro. Lupin and his friends leave Clarisse as Zenigata chases after them again and Fujiko makes off with the plates from the counterfeit printing presses.
Castle of Cagliostro, along with its title, includes elements that were seen in other Arsène Lupin works. One such tale, La Justice d'Arsène Lupin by Boileau-Narcejac, involves the discovery of a tremendous stash of forged franc notes with which World War I–era Germany had planned to destabilize the French economy. Maurice Leblanc's The Green-eyed Lady also featured a secret treasure hidden at the bottom of a lake. The castle is visually influenced by that of The King and the Bird (Le Roi et l'oiseau).
Optimum Releasing re-released Cagliostro in the UK after Manga Entertainment lost its license in the UK. The new DVD features an anamorphic widescreen print with the original Japanese audio track as well as the Streamline dub, both in stereo. Manga released a new special edition DVD of Cagliostro in 2006. The disc is double-sided with the film on side A and the extras on side B. It includes a new digital transfer; Manga's English dub in 2.0 and 5.1 surround plus Japanese, Spanish, and French language tracks in mono; the complete film in storyboard format, accompanied by Japanese audio with English subtitles; an original Japanese trailer; a sketch and still gallery; a 26-minute interview with animation director Yasuo Ōtsuka, and animated menus. The film is presented in 16:9 anamorphic widescreen; however, the opening credits have been heavily re-edited to remove the Japanese credits, instead using selected still-frames of scenes that appear without Japanese writing. The English-translated names are superimposed over these stills. (This modified credits sequence is also present on the 2007 Australian DVD release by Madman Entertainment.) In December 2008, the film was released on Blu-ray in Japan. Its video format is MPEG-4 AVC and its digitally-remastered audio is improved over that of the DVD. Optimum Releasing, now named StudioCanal, released a Blu-ray and DVD bundle of the film on November 12, 2012 in the UK.
The film was the best selling anime DVD in May 2001, and the third best selling in June. Both of Manga Entertainment's releases of The Castle of Cagliostro received DVD Talk Collector Series recommendation status, the highest status given by the review website DVDtalk.com. Chris Beveridge of AnimeOnDVD.com gave the film a grade of "A+", although he disliked Manga Entertainment's use of PG-13 level language in the English dub. The Castle of Cagliostro placed in 5th place on Japan's Agency for Cultural Affairs's list of best anime. The front of the cover for the second DVD release from Manga Entertainment cites an unverified praise for the film from filmmaker Steven Spielberg.
Gary Trousdale, co-director of Disney's Atlantis: The Lost Empire, admitted that a scene at the end of Atlantis, where the waters recede from the sunken city, was directly inspired by a similar scene from Cagliostro. One of the sequence directors of The Simpsons Movie also mentioned Cagliostro as an influence; the scene where Bart rolls down the roof was inspired by Lupin running down the castle roof during his rescue attempt. Cagliostro has also been influential for Pixar animator John Lasseter. Footage from this film, along with the previous Lupin film The Mystery of Mamo, appeared in the 1983 LaserDisc video game Cliff Hanger.
Lupin's car is a Fiat 500. A Fiat 500 was owned by Yasuo Ohtsuka, the head animator of the Lupin series. Clarisse was driving a Citroen 2CV, which was Miyazaki's first car. Zenigata's police car is a Nissan Bluebird. The truck Zenigata's men were using was a 1943 Canadian GM Military Pattern. In the car chase scene, the car driven by the MIBs (Men In Black) is a 1940 Humber Super Snipe. 
- Monaco casino security: M-3 "Grease Gun" (only seen for a couple of frames)
- Clarice chase mobsters: Thompson submachine guns and German "Model 24" hand grenades
- Jigen: Smith & Wesson Model 19 .357 Combat Magnum; Simonov PTRS-41 anti-tank rifle
- Lupin: Walther P-38 pistol
- Fujiko: Uzi submachine gun and Luger P-08 pistol
- Jodo & The Count (the autogyro escape scene): MG-34 machine gun
- Shadow guards at the wedding: Erma MP-40 ("Schmeisser") submachine gun
- Boat guards in the clocktower: fictional submachine gun combining elements from the Bergmann MP-18 (body) and the PPSh-41 (drum magazine)