Nefertiri was born in the 19th Dynasty of Ancient Egypt in 1265 BC. She grew up to be a very beautiful woman. She was later sacrificed to accompany Ramses to the afterworld. She woke up after her death an Immortal. She later met her teacher Raan, Priest of Osiris, who taught her everything about who she was. Nefertiri became a handmaiden to Cleopatra VII of Egypt, the most well known Queen regnant throughout history. Nefertiri fell in love with a Roman General named Marcus Constantine, who was also an Immortal. The war between Egypt and Rome was occurring at the time; the Egyptian empire was later defeated. Nefertiri became angry at what has happened to her people, she became angry at Marcus because she felt he had betrayed her, but claimed he still loved her. She raised her sword and she fought Marcus, but Marcus refused to kill her. Later on, Nefertiri was placed in a sarcophagus in which she would be in for the next 2,000 years.
Two millennia have passed now. The year is 1994, Nefertiri is now in Paris, France still in her sarcophagus until it is opened by another Immortal, Duncan MacLeod. She is very shocked to see how things have changed. Duncan teaches her about the new world she has entered and he takes her to a museum to show her the history that has happened since she was gone for 2,000 years. At the museum, they sense the presence of another Immortal - it is Marcus Constantine, the curator of the museum. Nefertiri asks Duncan for a sword thinking that he is coming for her head and runs out. Duncan meets Constantine; they talk about the past and Nefertiri.
Later on, Duncan has Nefertiri talk to Constantine, she is still angry at Marcus, thinking he betrayed her. Duncan and Nefertiri have dinner at the barge, Maurice cooked dinner for them, Maurice goes to get something. A man named Victor Benedetti, who works for Marcus Constantine, is a member of the Hunters, a group of renegade Watchers. He tries to take Nefirtiri's head, but she kills him. Duncan gets back and sees the dead man. He goes to the body and sees a Watcher's tattoo on his wrist. Duncan dumps the body into the Seine River. Later on, Duncan and Nefertiri go to the museum and talk with Constantine. He tells Nefertiri that he still cares about her and her happiness and he invites her and Duncan over for dinner. When they arrive, Constantine introduces his wife, Angela. They all have dinner and Angela goes to the kitchen alone. Nefertiri goes to talk to her and picks up a knife and stabs her, killing her. Nefertiri tells Constantine to "be happy". At the barge, Duncan has Nefertiri leave because of her actions. Nefertiri is angered at Duncan, thinking after he made love to her, he is throwing her out.
The next day, after Angela's funeral, Nefertiri is there to take Constantine's head, but Duncan stops her. She challenges him to fight cause she thinks that Duncan betrayed her, too. They fight with their swords and enter a building. Nefertiri stabs MacLeod, but Duncan takes her head and receives her Quickening.
Since Nefertiri opened her eyes in the 20th century, she should not have been able to speak English at all. Her spoken languages would have included New Kingdom Egyptian, Late Egyptian/Demotic, and since she was in the court of Cleopatra, Hellenic Greek.
Catherine Zeta Jones auditioned for the part of Nefertiri before Nia Peeples won it.