Isabella "Bella" Swan is given an eighteenth birthday party from Edward Cullen, the vampire whom she loves, and his entire vampire family consisting of Carlisle, Esme, Rosalie, Emmett, Jasper, and Alice. Bella accidentally gets a paper cut there, and this leads to a violent and tense moment. Jasper, the newest member of the 'family' to try out the non-human diet, cannot contain himself at the sight and smell of her blood and makes a leap for Bella. Edward is forced to protect her, but this makes it all too clear that keeping Bella close to the family puts her at risk. In the midst of this, a pivotal moment occurs during a conversation with Carlisle while cleaning her wounds. Bella is told that Edward believes that vampires are soulless creatures and that there is no better place for them if they die. It is made clear that Edward's relationship with her is a constant tug of war in his heart because he doesn't want to risk turning Bella into a creature who he believes is damned. Edward begins to withdraw himself emotionally, and later he and his family depart from Forks in an attempt to keep Bella safe. He unknowingly hurts Bella further by taking photos and memories that would prove his existence, in an attempt to make a clean break of their relationship.
Bella becomes severely depressed and withdrawn from the world after his departure. She enters a state of mourning and months go by where she is just going through the motions of everyday life without actually experiencing any of it. Eventually she realizes how this is affecting her dad and attempts to pull herself together for his sake. On an outing with a friend, Bella finds herself in a potentially dangerous situation and finds that she can hear Edward's voice in her mind. She prolongs the situation and can hear Edward during the entire episode which makes her pain of losing him more bearable. Bella finds that she can always hear Edward if she is in potential danger and, because of this, becomes increasingly reckless.
Jacob Black, the young Native American from Twilight, makes a reappearance in New Moon. Bella finds two motorcycles on the side of the road that need work and she remembers that Jacob is a mechanic of sorts. She loads them onto her truck and offers Jacob one of them as payment if he can make them run. They become very close friends and Bella depends on him, filling up the hole in her heart as best as she can with their friendship. Jacob is attracted romantically to Bella and although Bella knows this and tells him they are just friends, there is nothing uncomfortable about their closeness. They have such a tender regard for one another despite, or maybe because of, Jacob being the complete opposite of Edward; awkward, humanly attractive (as opposed to Edward's supernatural looks) and warm-blooded.
In the midst of their growing closeness, Jacob confides in Bella that something is going on at La Push reservation. Jacob confesses that he is afraid of Sam Uley, the leader of a group of older guys on the reservation. A friend of his had expressed fear of the group, went missing for days, and then resurfaced as a member of the gang. He has been acting strangely and Jacob believes they are up to no good. He is also frightened that he could be next on the list.
During an outing with Jacob he becomes very ill and fevered. After this episode Bella finds it is almost impossible to get in contact with Jacob before finding that he has reappeared as a follower of Sam Uley. Bella confronts him at his house and Jacob harshly tells her that he must stay away from her and never see her again. However, after a fight ensues, Jacob clearly hurting and regretful sneaks into her room late at night to tell her that she knows exactly what is happening to Jacob, she just doesn't realize it. The only clue he gives her is reminding her of the legends he told her when they first met.
Bella eventually recalls a story about werewolves and vampires and realizes that Jacob, and the rest of Sam Uley's gang, are indeed werewolves, and thus the enemies of her beloved Cullens. This presents a whole new set of problems for Jacob and Bella, because not only is there animosity between Jacob and Edward because of their mutual love for Bella, but they are also sworn enemies because of what they are. There is genuine potential for bloodshed and the possible death of either at the other's hands.
Things are further complicated by the return of Victoria. Victoria seeks to avenge her mate, the vicious tracker vampire James, whom Edward killed after James attempted to kill Bella. Rather than kill Edward, Victoria sees killing Edward's "mate" as a fair trade. It is up to Jacob and his pack to protect Bella from Victoria's revenge.
The climax of the story leads Bella on a rescue mission to save Edward after he is misinformed of Bella's supposed suicide when she was actually cliff-jumping. He makes a trip to Italy, home of the dangerous and ancient Volturi vampires, in the hopes that they will kill him. Alice accompanies Bella to Italy and during their trip she receives flashes of what is happening with Edward and the Volturi. Seeing how valuable an asset Edward would be, the Volturi refuse to destroy him and invite him to join their coven. He refuses and devises a plan to walk out into the middle of the city at noon with his skin exposed in order to force the Volturi's hand. A vampire's skin, when exposed to the sun, glitters like diamonds, which would expose him and potentially, the Volturi. Bella and Alice arrive in time to stop him from stepping into the sunlight, but are cornered and escorted to the underground home of the Volturi by vampires working for them. It is here that we find that even the eldest of the clan are not able to penetrate Bella's mind and that any powers that the vampires might possess will do them no good when it comes to her. The Volturi tell Edward that Bella cannot leave because she is a human who knows their secret and that is not allowed. Bella, Edward, and Alice make a deal with the Volturi; they agree that in the near future they will turn her into a vampire in order to prevent them from harming her. They agree, with the assertion that they will be paying a personal visit in order to ensure the deed is done. The group is allowed to leave, but upon returning to America, Edward refuses to turn her right away. He wants to wait until it is absolutely necessary, which could take years. Bella then brings the decision to Edward's family who have returned to Forks. They take a vote and all but Rosalie agree on the decision to turn Bella into one of their family. Bella eventually convinces Edward into turning her after she agrees to Edward's compromise; that she finish high school, and that they get married beforehand. Returning home, Bella finds Jacob waiting for her and there is a showdown between Jacob, Edward and Bella. Jacob tells Bella that they cannot be friends with Edward in the middle, while also reminding Edward that if he bites a human he will be breaking their treaty, which would leave their coven open to attack by Jacob and his pack. The story ends with Bella determined to find a place for Jacob in her life while also dealing with her desire to be a vampire.