Where on Earth is Carmen Sandiego?

When Carmen attempts to steal several items having to do with military strategies, she is foiled several times by 'The Tigress', a thief with a lot of high-tech weaponry of her own. The Tigress lures Carmen to Antarctica, where she reveals herself to be Ivy in disguise. Carmen was ambushed by Acme detectives and taken away, but escapes when she steals Ivy's CO2 boots Zack invented.

While chasing after Carmen, Zack and Ivy discover that Carmen was an orphan. They trail her to the Golden Gate Girls' School which is about to be torn down.

Zack and Ivy manage to capture Carmen in Hawaii. However, Zack loses his lucky rabbit's foot and begins to believe he's cursed with bad luck. Meanwhile, Carmen escapes and tries to teach her superstitious henchwoman, Hannah Lulu that there's no such thing as curses or ghosts. Hannah has a panic attack though when Zack and Ivy scare her at a supposedly haunted site. They manage to capture her but Carmen escapes. She leaves behind something Zack was glad to see again - his lucky rabbit's foot.

Somehow, the world's largest diamond, the Star of Africa, was stolen. The police are baffled and it's up to Zack and Ivy to figure this mystery out. They soon discover that one of Carmen's henchmen tried to double-cross her and keep the diamond for himself. With a little trickery of their own, the detectives recover the diamond.

Carmen's reoccurring nightmare sends to her to seek the help of three Native American shamans to interpret it. Meanwhile, Zack, Ivy and a Native American detective named Billy 'Running Bird', track Carmen to Devil's Tower where the meaning of her dream is revealed. Though Carmen is captured, the shamans let her go. They do not want to go back on their promise - they would interpret her dream in exchange for the return of the items she stole from them.

It is reported that Carmen dies in a plane crash. The grief-stricken Chief is unable to help Zack and Ivy solve a series of clues that Carmen left behind to a final caper. The henchman who solves the most of them will be the new leader of V.I.L.E. Zack and Ivy manage to stop all of the thefts. They then travel to the site of Carmen's reported death to pay their last respects. Suddenly, a little bird delivers a message to "look up". When they do, they see Carmen was alive all that time. She had planned to fake her death to see who was worthy enough to take her place - and it turns out Zack and Ivy are the only ones who can!

Zack and Ivy discover Carmen's underground training facility and go undercover as henchmen in training to try and nab Carmen. However, Carmen discovers them and leads them to a chamber that seems to have no way out. There is one way - an escape into time. Carmen created another time machine and uses it to escape. The detectives use a new Chronoskimmer that the Chief gives them and they trace where Carmen is heading - the future.

Carmen arrives in the year 2101 where she stops a heist of a powerful electro-magnet. Meanwhile, Zack and Ivy arrive at the future Acme Detective Agency where the wacky Future Chief doesn't recognize them. They try to prove who they are but run into a few scrapes with the law. Eventually, they meet up with Carmen in Africa. Although the detectives expose that she is a criminal, she escapes with the magnet and Zack and Ivy end up captured instead.

Zack and Ivy escape from the future and follow Carmen to Rome. There, the detectives are captured and are sentenced to fight each other in the Colosseum games. Luckily, they are spared from having to fight each other to the death. They escape, and discover Carmen's plan - she's going to steal the Colosseum! The detectives realize this is part of her plan to become 'the greatest thief of all time' by stealing objects from the past, present, and future.

Carmen gives herself a Christmas present by downloading The Chief. Only he's got a virus and is losing his memory. He thinks that Carmen is still good and that Zack and Ivy are thieves.