Plot
Before school starts

Voldemort and his Death Eaters openly wreak havoc and chaos throughout Britain. Following public outcry over Cornelius Fudge's mishandling of the Voldemort situation, he is forced to resign, and is succeeded by Rufus Scrimgeour as the new Minister for Magic. As a result, Arthur Weasley receives a promotion.

At his home in Spinner's End, Severus Snape receives a visit from Draco Malfoy's mother Narcissa and her annoyed sister, Bellatrix Lestrange. Narcissa swears Snape to an Unbreakable Vow, ensuring he will protect Draco during his task assigned by the Dark Lord and, should her son fail, complete his mission for the Dark Lord.

Albus Dumbledore arrives at the Dursleys' and asks Harry Potter to accompany him to see retired professor Horace Slughorn. With unwitting help from Harry, Dumbledore persuades Slughorn to resume his old teaching post at Hogwarts. Harry then spends the remaining summer months at The Burrow with the Weasleys and Hermione, who is also visiting. To his family's dismay (mainly Ginny, Mrs Weasley, and Fred & George), Bill Weasley has become engaged to Fleur Delacour, the Beauxbatons champion in the Triwizard Tournament. During this summer Harry spends time with Ginny and experiences the stirring of feelings for her. Harry, Ron, and Hermione receive their O.W.L. results. Hermione receives high marks in all her subjects, but Ron and Harry fail Divination and History of Magic. They are also unable to take N.E.W.T.-level Potions because Snape only accepts "O" (Outstanding) grades. The course is a requirement to Harry's ambition of becoming an Auror. While in Diagon Alley buying supplies for their upcoming year at Hogwarts, Harry, Ron and Hermione spot Draco Malfoy sneaking off into Knockturn Alley, where they follow him and spy on him. They see him enter Borgin and Burkes, a dark magic shop, and witness him harassing Mr Borgin about repairing one item and keeping another safe for him.

At Hogwarts

As school begins, Snape is unexpectedly announced as the new Defence Against the Dark Arts instructor, while Slughorn takes his place as the Potions teacher. Since Slughorn only requires a minimum "E" grade (Exceeds Expectations) at O.W.L. to take his N.E.W.T.-level Potion classes, Harry and Ron are now able to sign up. Not having expected this, they haven't bought any teaching material beforehand, and so Slughorn lends them old Potions textbooks. Harry's copy is marked as the property of "The Half-Blood Prince." The talented former owner's handwritten notes help Harry excel in the class. As a reward, Slughorn gives him a small vial of Felix Felicis, a good luck potion.

As the year progresses, more Death Eater attacks occur which may be linked to events happening at Hogwarts. On the first Hogsmeade visit, Katie Bell, a Gryffindor student, is seriously injured when she is forced to carry a cursed necklace while under the Imperius Curse. Harry suspects Malfoy or another Death Eater is involved. In another incident, Ron is accidentally poisoned when he drinks mead that was intended for Dumbledore — Harry's quick thinking saves his life when he forces a bezoar, a poison antidote, into his mouth. Prior to this Ron and Hermione had engaged in a vicious feud wherein Ron had dated Lavender Brown mostly to annoy and anger Hermione for having kissed Viktor Krum, and Hermione had retaliated by using Cormac McLaggen as her date for Slughorn's Christmas Party, which backfired so horribly on her that even Harry chastised her for her behaviour. Ron and Hermione's continual bickering had caused Harry to fear they would never reconcile. However, Hermione is so upset and distraught over Ron's near poisoning that she reconciles with him, and Ron eventually breaks up with Lavender. In the meantime, Harry discovers the real nature of his feelings for Ginny, now the Quidditch team's Chaser, when he jealously observes her kissing her boyfriend, Dean Thomas. However, Harry hesitates to do anything because of Ginny's relationship with Dean and a fear that Ron would not react well to Harry dating his only sister.

Horcruxes

Dumbledore begins tutoring Harry privately, using his Pensieve to view collected memories about Voldemort's past. A memory belonging to Slughorn is partially missing. Aided by the Felix Felicis potion, Harry retrieves it from him. Dumbledore speculates that Voldemort has split his soul into seven fragments, storing six pieces in Horcruxes to grant himself immortality, while leaving the seventh in his own body. Two Horcruxes have been destroyed (Tom Riddle's diary by Harry[HP2] and Marvolo Gaunt's ring by Dumbledore).

When Harry finds Malfoy sobbing in Moaning Myrtle's bathroom, they begin hurling curses at each other. Harry casts Sectumsempra (a spell gleaned from the Half-Blood Prince's annotations), causing large gashes across Malfoy's body. Snape arrives and saves Malfoy. Recognising the spell, he orders Harry to hand over his Potions book. Harry instead gives him Ron's copy. Snape assigns Harry detention every Saturday for the remainder of the term, and incidentally, the first of which is on the same day as the Quidditch finals. After detention, Harry learns that Gryffindor has won the finals, with Ginny Weasley as their substitute Seeker. During the victory celebration, Harry's suppressed feelings for Ginny are revealed when he spontaneously kisses her; Ginny had broken up with Dean Thomas several days before, and she and Harry begin dating.

Harry has suspected all year that Malfoy may be a Death Eater and has confided his suspicions to Dumbledore, who seemed unconcerned. He learns later that Dumbledore had Snape investigate Malfoy. One day, Harry learns from Professor Trelawney that it was Snape who had passed information to Voldemort about Harry's parents fifteen years before; enraged, Harry confronts Dumbledore about trusting Snape after what he had done. Dumbledore stands firmly with his argument of unknown evidence and then brings Harry up to date by informing him that he has learned the location of one of the Horcruxes, and invites Harry to accompany him in retrieving it. Believing Malfoy and Snape are involved in something sinister, Harry asks Ron, Hermione, Luna Lovegood, Neville Longbottom and Ginny to patrol the halls while he and Dumbledore are gone and gives them the remaining Felix Felicis potion to keep them safe. Harry then disapparates with Dumbledore to a secret cave. Upon retrieving the Horcrux (seemingly, Salazar Slytherin's locket), Dumbledore is seriously weakened by a potion he drank in order to uncover the locket inside a basin.

Battle at Hogwarts

Returning to Hogsmeade, Harry and Dumbledore see Lord Voldemort's Dark Mark hovering over Hogwarts. They borrow broomsticks from Madam Rosmerta, whom they later discover to be under the Imperius Curse of Malfoy. They fly to the Astronomy Tower where they are ambushed by Draco Malfoy. Dumbledore paralyses Harry, who is under his Invisibility Cloak, just before Draco disarms Dumbledore. Draco reveals that he helped the Death Eaters enter Hogwarts via a vanishing cabinet located in Knockturn Alley and Hogwarts, although Dumbledore discerns that the obviously frightened boy was coerced into aiding Voldemort's followers. In the meantime, members of the Order of the Phoenix (including Remus Lupin, Nymphadora Tonks, Professor McGonagall, and Bill Weasley) battle the Death Eaters down below in the main school.

Death Eaters appear on the Astronomy Tower where the Dark Mark is and urge Draco to fulfill his mission — killing Dumbledore — but Draco is reluctant and apparently scared. Snape arrives; still weak from the potion, Dumbledore entreats Snape with an ambiguous plea. Snape kills Dumbledore with the Avada Kedavra killing curse. The spell's force hurls Dumbledore's body over the tower wall. Upon Dumbledore's death, Harry is freed from the paralysing spell. The Death Eaters flee, and Harry pursues Snape, who identifies himself as the Half-Blood Prince in a short-lived duel before escaping with Malfoy. Snape also states that Harry doesn't have the strength to defeat him and is weak just like his father, enraging Harry even more.

Harry recovers the locket from Dumbledore's body only to discover that it is a fake. Inside is a note from someone with the initials "R.A.B." who has stolen the real Horcrux and has vowed that it will be destroyed with the hope that when Voldemort meets his match he "will be mortal once more".

The school year ends abruptly with Dumbledore's funeral, which is attended by hundreds of people, including the students past and present, teachers, and magical creatures that live in the Forbidden Forest. Professor McGonagall is appointed Hogwarts' interim headmistress, although the school may not reopen. Professor Slughorn replaces Snape as the head of Slytherin house. Regardless, Harry decides to leave Hogwarts forever to search for the remaining Horcruxes. Ron and Hermione vow to accompany him, while Harry ends his relationship with Ginny in an attempt to protect her from Voldemort. The book concludes as Harry looks forward to Bill and Fleur's wedding and being comforted that "...there was still one last golden day of peace left to enjoy with Ron and Hermione."