Danny meets his evil opposite in Vlad Plasmius, a childhood rival of his ghost-hunting dad, Jack. Unfortunately, Vlad acquired ghostly powers 20 years ago, which means he's stronger and more experienced than Danny -- and hell-bent on taking everything away from Jack Fenton including his life.

Maddie relishes the chance to bond with emotionally distant Danny at a weekend mother/son science seminar. However, the seminar is a ruse orchestrated by Vlad Masters - a.k.a. Vlad Plasmius, Danny's arch enemy! Vlad's plan is to convince Maddie and Danny to live with him while simultaneously destroying Jack with a massive ghost attack. When Vlad short-circuits Danny's powers, Danny gets to witness Maddie's impressive ghost fighting prowess. Meanwhile, a reluctant Jazz is pressed into ghost-fighting duty with Jack - and likes it, in spite of herself!

When Vlad Masters' ghost portal explodes, he schemes to replace it by stealing Jack Fenton's portal. As a distraction, Vlad anonymously offers a million dollar bounty to eliminate Danny Phantom. As ghost hunters from around the world gather in Amity Park to hunt the ghost kid, Danny sacrifices himself to Jack - both to win the prize money for Dad and to bolster Jack's inept reputation, which embarrasses Danny. However, when his family's life is put in jeopardy, Jack needs no help from Danny to save the day on his own.

Skulker's on a looting spree, snatching up a number of seemingly unrelated items. Unfortunately, Danny's attempts to stop him are thwarted by the well-intentioned meddling of Danny's new sidekick: Jazz. However, Danny didn't ask for -- and doesn't want -- Jazz's help, and after a series of humiliating mishaps, Danny blows up at his sister. In response, Jazz runs away from home... to Vlad's castle in Wisconsin! But it's only a ruse. Jazz soon manages to break into Vlad's inner sanctum and discovers that he has been using Skulker to collect the items necessary to upgrade the Fenton's stolen Ecto-Skeleton. When Danny arrives at the castle, Vlad makes Jazz don the improved battle suit in a no-holds-barred fight against Danny Phantom!

Vlad is back, only now he's afflicted with a serious case of ecto-acne, a direct result of the college lab accident with Jack and Maddie. To ensure Danny helps him find a cure, Vlad infects Sam and Tucker with his disease, and Danny turns to Clockwork for help. Danny convinces Clockwork to let him go back in time to make sure the accident that injures Vlad never happens. Unfortunately, when he changes the past, he changes the present. When he arrives back in the present day, Maddie is married to Vlad and living in Wisconsin, and Jack's a ghost named Jack Plasmius! Now, Danny must go back in time for a second time to ensure his parents get together, but when he does, will that mean ecto-acne doom for Tucker and Sam?

Vlad's up to something and it involves Danny. After he sends three ghosts to Amity Park to battle Danny Phantom, it is revealed that he's working on his creepiest project yet: a clone of Danny Phantom. So far, the clones he creates can't sustain their forms for very long, but Vlad is determined to succeed. Danny doesn't have long to worry about Vlad's ghostly visitors, however, because he's distracted by the appearance of Danielle, a cousin he didn't know he had. And then, Danielle reveals that she too has ghost powers -- she's Dani Phantom! Unfortunately, she's also a product of Vlad's experiments, and therefore an imperfect ghost with an unstable form. Danny must convince his new "relative" to turn on her creator and help him destroy Vlad's evil experiment, before it's too late for both ghost kids.

After getting lost in the ghost zone, Danny and his friends find in a frozen zone the Infimap, a map that lets the holder to travel everywhere in the ghost zone. After Vlad Masters steals the map, Danny, Sam and Tucker must chase him through different times and places, from Salem to ancient Rome, to get this treasure before he manages to conquer Earth.

Amity Park is in the midst of a drought, and Mayor Vlad, eager to score points, releases Vortex, the weather ghost, to make it rain. But when Vlad double crosses Vortex, the ghost conjures a storm that threatens to drown the town! As Danny Phantom flies to the rescue, he’s zapped by a lightning bolt. When he comes to, he discovers that his emotions are now directly tied to the weather!

The Fentons sell Fenton Works to the Guys in White who plan to destroy the Ghost Zone (unaware that Earth will be destroyed too) with a missile; meanwhile, Danny starts to let the rich life get a hold of him and jeopardize his friendship with Sam and Tucker.

Danny and Vlad’s game of revenge against each other begins with childish pranks, and, unfortunately for Danny, ends when Vlad decides to run for mayor of Amity Park! By overshadowing voters, Vlad wins in a landslide. The new mayor is eager to use his new power to make life as miserable as possible for Danny and his friends. He shuts down the Nasty Burger, outlaws technology, creates new school uniforms, and passes so many new laws in the name of “protecting the children” that Danny finds it impossible to go ghost.

Dani Phantom has finally returned to Amity Park. Having the trouble of dissolving into nothing worst than ever, she seeks the one person who can help her, her cousin and best friend, Danny Phantom! However, Vlad has been keeping track of her since her last appearance and plans to get his "little girl" back, by duping Valerie Gray into doing it for him. After finding Danielle, she uses her to lure Danny into a trap and now she has two Danny Phantoms trapped! Now stuck in the clutches of Valereie Gray, Danny must find a way to escape and save his cousin from being melted to ectoplasm by Vlad!

Danny, after being publicly shamed by Vlad's new ghost hunting team, wants to be normal again. So he gets rid of his powers by reactivating the Fenton Portal after Jack dismantles it for a software upgrade. However, an asteroid made of Ectoranium threatens the Earth, and Vlad - after revealing to everyone that he is Plasmius - fails to stop it. The world now relies on a powerless Danny to get help from the ghosts in the Ghost Zone!