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.

The building boom in Amity Park upsets Undergrowth, the ghost of all things plant-like and vegetative. The green-thinking ghost takes over the town, turning everyone into plants themselves. All except Sam, that is, whom he makes his Earth-loving queen. Unfortunately, Undergrowth brainwashes Sam and uses her to attack Danny! Danny, meanwhile, has been battling a nasty case of the chills that leaves him too weak to fight. Escaping from Undergrowth in the Ghost Zone, Danny turns to his cold-loving friend, Frostbite,who explains that Danny is developing a new power. Now, Danny must learn to master his new freezing skill so that he can make his way back to Amity Park and pull the town out of Undergrowth’s leafy clutches.

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!

Amorpho, a ghost with morphing abilities, impersonates people and gets them into trouble with it. He then impersonates Danny and both of them must learn the price of fame when a fenton device interrupts some of their powers, preventing Danny from returning to his human self and locking the evil shapeshifter in a shape that calls too much attention: Mr. Lancer's.

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.

As one of the weakest ghost in the Ghost Zone, the Box Ghost attacks with every "deadly box" he has in the human world, but is easily defeated by Danny. He then makes a plan: he will use "Pandora's Box", the most powerful box ever created, and will use the evil and deadly powers inside it to attack Amity Park. Now Danny must find the only one able to save the day: Pandora herself!

Danny wakes up wearing a strange headset in the Ghost Zone. He returns to Amity Park and discovers everyone is asleep thanks to the ghost of sleep, Nocturne, who is sucking up their dreams to increase his energy. Danny must wake his friends and sister in order to stop this threat.

Danny's class goes to a camping trip with Mr. Lancer and Ms. Teslaff to an abandoned place which is seemingly haunted. Soon reports of monster sightings and missing students have the whole camp shook up. Monsters start showing up and disrupting the camping trip. To Danny's surprise, these monsters are ghosts working for Walker, on the hunt for Wulf. Now Danny must save his old friend and his class from Walker!

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!