Season 1: Nick discovers his Grimm heritage while investigating a series of killings. He teams up with Monroe. Adalind Schade, a Hexenbiest working for Captain Sean Renard (who is secretly a half-royal Zauberbiest), attempts to kill Aunt Marie and poisons Juliette with a scratch from a Wesen cat. Aunt Marie dies, leaving Nick her trailer full of lore. In the finale, Juliette slips into a mystical coma, and Nick's presumed-dead mother, Kelly Burkhardt, arrives in Portland.
Season 2: Juliette wakes from her coma with amnesia, unable to remember Nick while uncontrollably drawn to Captain Renard due to a purification spell. Nick reveals the truth about Wesen to Hank. Adalind escapes to Europe to regain her stripped Hexenbiest powers by getting pregnant by a Royal (Prince Eric). A Haitian Wesen (Baron Samedi) turns civilians into zombies and infects Nick, shipping him in a coffin to Europe.
Season 3: Nick breaks free from his zombie fugue state, gaining residual physical enhancements (superhuman hearing and heart-rate control). Adalind gives birth in Europe to Diana, a child of extraordinary telekinetic power, and escapes with the help of resistance fighter Meisner. Nick takes in a runaway Grimm, Theresa "Trubel" Rubel. In the finale, Adalind uses a transformation potion to disguise herself as Juliette and sleep with Nick, robbing him of his Grimm powers just as Monroe and Rosalee marry.
Season 4: Nick remains human while Trubel acts as his eyes. To restore Nick’s Grimm powers, Juliette undergoes a complex ritual, which triggers an unexpected side effect: she turns into an extremely volatile, pureblood Hexenbiest. Driven mad by her transformation, Juliette aligns with the Royals, helps orchestrate the ambush and decapitation of Nick’s mother Kelly, and burns Aunt Marie's trailer. Trubel shoots Juliette with a crossbow to save Nick’s life. Meanwhile, Adalind discovers she is pregnant with Nick’s child.
Season 5: Adalind gives birth to Kelly and moves in with Nick for safety, gradually developing genuine feelings for him. Juliette is revealed to be alive, saved and reprogrammed by the covert government anti-Wesen terrorist group Hadrian's Wall as an emotionless operative named "Eve". A global Wesen supremacist movement called Black Claw rises, recruiting Captain Renard to run for mayor. Nick recovers a piece of the Crusaders' treasure in Germany: a mystical wooden stick possessing miraculous regenerative healing powers.
Season 6 & Series Finale: Renard backs away from Black Claw after political collapse. An inter-dimensional demonic entity named Zerstörer ("The Destroyer") emerges from a mirror world, seeking Diana as his child bride and the healing stick to complete his apocalyptic staff. In Portland, Zerstörer massacres the entire police precinct (killing Hank and Wu), and systematically murders Eve, Renard, Adalind, Rosalee, and Monroe. Refusing to yield the staff, Nick is joined by the spectral spirits of his mother Kelly and Aunt Marie. Together with Trubel, the four Grimms fight and slay Zerstörer. As Zerstörer disintegrates, Nick is pulled through the portal back to the exact moment he first stepped out: all of his friends and loved ones are alive and well, completely unaware of the massacre that just occurred. The show jumps forward 20 years to the trailer: an adult Kelly Burkhardt is writing in the ancestral Grimm journals alongside his sister Diana and Monroe and Rosalee’s triplets, heading out to fight Wesen threats together.