Severus Snape, a member of the Order of the Phoenix, meets with Narcissa Malfoy, Draco’s mother, and her sister Bellatrix Lestrange, Lord Voldemort’s faithful supporter. Narcissa expresses concern that her son might not survive a dangerous mission given to him by Lord Voldemort. Snape makes an Unbreakable Vow with Narcissa, swearing to assist Draco.
Dumbledore picks Harry up from his aunt and uncle’s house to escort him to the Burrow, home of Harry’s best friend Ron Weasley. They detour to the home of Horace Slughorn, former Potions teacher at Hogwarts, and Harry unwittingly helps persuade Slughorn to teach.
On the Hogwarts Express, Harry discusses his suspicions of Draco’s allegiance with Voldemort to a sceptical Ron and Hermione. Using his invisibility cloak, Harry eavesdrops on Draco in this carriage, overhearing him bragging to his friends about the mission Voldemort has assigned him. Draco catches him in the process, petrifying him and breaking his nose. Nymphadora Tonks finds Harry and escorts him to the castle, where Dumbledore announces that Snape will be teaching Defence Against the Dark Arts, while Slughorn will be Potions master.
Finding an old textbook that once belonged to “The Half-Blood Prince”, a mysterious individual who excelled at Potions and wrote numerous spells and tips in the book, Harry excels at the subject as well, eventually winning a bottle of Felix Felicis, or “Liquid Luck”. Though Harry’s success pleases Slughorn, his underhanded methods anger Hermione, who also distrusts the Prince.
Ron and Hermione grow closer, but after learning from his sister Ginny of Hermione’s history with Viktor Krum, Ron goes out with Lavender Brown, making Hermione jealous. Harry develops feelings for Ginny, and despite his reluctance to pursue her due to his friendship with Ron, the two later start a relationship with Ron’s approval after a Gryffindor Quidditch victory. Draco grows increasingly unhinged throughout the year, culminating in a duel with Harry. In the duel, Harry uses an unknown spell from the Prince which nearly kills Draco, although Snape saves him.
Meanwhile, to help Harry in his foretold battle with Voldemort, Dumbledore and Harry use Dumbledore’s Pensieve to examine memories of people who had met Voldemort before. One of the memories involves Slughorn conversing with a young Tom Riddle at Hogwarts, but it has been tampered with, so Dumbledore asks Harry to obtain the real memory from Slughorn. Harry uses Felix Felicis to retrieve the memory, in which Slughorn tells Riddle about the process of splitting one’s soul and hiding it in Horcruxes, making the user virtually immortal. Voldemort created six Horcruxes, which must be destroyed in order to destroy Voldemort himself. Two Horcruxes, Riddle’s diary from Harry Potter and the Chamber of Secrets and a ring belonging to Voldemort’s grandfather, have already been destroyed; four others remain.
Near the end of the year, Harry and Dumbledore journey to a cave to retrieve a suspected Horcrux, Slytherin’s locket. They find the locket in a potion-filled basin in the middle of an underground lake. As the locket can only be reached by drinking the potion, Dumbledore does so, severely weakening him. After fighting off Inferi, which were hiding in the lake, Harry and Dumbledore take the locket and return to Hogwarts, to find that the Dark Mark has been placed over a school tower. They ascend the tower and are ambushed by Draco who reveals that his mission from Voldemort is to kill Dumbledore, and has helped Death Eaters get inside Hogwarts. However, Draco cannot go through with it. Snape arrives and kills Dumbledore instead. Harry ignores the battle raging in Hogwarts to pursue Snape, but is defeated by him, who reveals himself to be the Half-Blood Prince before escaping with Draco and the other Death Eaters.
After Dumbledore’s funeral, Harry breaks up with Ginny, believing it to be too dangerous to continue their relationship. He discovers that the locket is a fake, containing a note from someone named “R. A. B.”. Harry announces his intentions to search for Horcruxes the following year rather than return to Hogwarts.