Nicholas Burkhardt is the show's protagonist and titular Grimm. Nick is a homicide detective who discovers he is descended from a line of Grimms, hunters who fight supernatural forces. Even before his abilities manifested, Nick had an exceptional ability to make quick and accurate deductions about the motivations and pasts of individuals, which has now expressed itself as his ability to perceive the supernatural that nobody else can see. Nick had wanted to propose to his girlfriend, Juliette, for a while, although he felt that he would have to tell her about his life as a Grimm beforehand.

Nick struggles to maintain balance with his normal life and his Grimm life, both tending to cross when he works cases that involve Wesen, the creatures of the Grimm world. As Nick dives deeper into his Grimm heritage, he begins to train with Monroe to use the weapons that his aunt Marie left behind, as well as increase his knowledge of the Wesen that are present in Portland. As of episode 19, Nick has successfully killed three Reapers, creatures sent out to kill Grimms (hence the Grimm Reaper title). He killed the first in defense of Marie, and the other two were killed in self-defense when they were sent to kill him by his lead suspect in a case. The latter two had their heads cut off and sent back home (with a note saying to send the best next time). In the season finale, Nick's worries about the scratch Juliette received from Adalind's cat forced him to reveal his Grimm heritage to her, causing Juliette to believe he has gone crazy. When bringing her to the trailer was not enough to convince her, they go to Monroe's house so that Nick can show her his Blutbad form, though before Monroe could show her, Juliette collapsed and was brought to the hospital.

Rosalee discovers that Juliette is going through memory loss, and when Juliette wakes up it is revealed that the only thing she has forgotten is Nick. Nick, after believing for eighteen years that both of his parents died in a car crash, discovers in the first episode of season two that his mother is alive and well, but he is still unaware of her true motives and full agenda.