
A group of ghostly skeletons under the command of a bratty 10-year-old pirate named Youngblood attacks FentonWorks and steals the ghost shield. Soon after, all the adults in Amity Park are packing for a cruise without their kids. Danny, Sam, and Tucker discover that the cruise is a hoax and the adults are under the spell of a mysterious (and cheesy) song created by Ember to make them into galley slaves for Youngblood's pirate ship! The stolen ghost shield prevents Danny Phantom from getting on board the ship, so Danny Fenton has to lead Amity Park's teenagers in a daring attempt to save their parents.
Danny and Sam get into a fight, and when Sam utters the words, "I sometimes wish I'd never met you," she finds herself in a world in which she and Danny are strangers. Worse than that, since it was Sam who encouraged Danny to check out the Fenton Portal the night he got his ghost powers, Danny doesn't have any powers! Now, Sam must convince Danny that they share a friendship and a history, and lead him back to the Fenton Portal for a second "accident" so he can again become Danny Phantom.
After being bitten by tiny green ghost beetles, the kids of Casper High get a mysterious illness that gives them ghost powers and are quarantined at a spooky old hospital outside of town. When Danny sneaks into the hospital to investigate, he is captured by Penelope Spectra and her assistant, Bertrand. They are the ones who started this illness as part of their plan to build Penelope a young and beautiful new body. All she needs is Danny's half-human/half-ghost DNA to complete her ghostly plan. With Danny captured and Sam sick, it's up to Tucker to conquer his fear of hospitals and free Danny before Penelope gets what she's after.