The game begins in London where it is revealed that Snape made the unbreakable vow with Narcissa Malfoy, Draco's mother. Meanwhile, the wizard world is in crisis over the antics of the Death Eaters, Voldemort's followers. Harry spends some time at the Burrow, where after a broom ride he discovers his affection for Ginny Weasley. Harry starts to think that Draco Malfoy has become a Death Eater, which leads to Harry spying on him on the train ride to Hogwarts. Malfoy finds Harry, and paralyzes him until he is rescued by Luna Lovegood. When Harry first enters Hogwarts, he discovers that Snape has become the defence against the dark arts teacher.
Harry attends his classes, participates in the dueling club, and plays on the Gryffindor Quidditch team like any other student. His Potions book is second hand, and at one time belonged to the Half Blood Prince. The potions book is modified with different instructions, which result in better potions and the admiration of Slughorn, but the jealousy of Hermione.
The potions book also contained the spell sectumsempra. When Harry used the spell on Draco, it injured him, guilting Harry to hide the book in the room of retirement. Ron Weasley stars to date Lavender Brown, to Hermione's distaste, which leaves Harry caught in the middle of their conflict. Harry meets with Albus Dumbledore to learn more about Voldemort's life, mostly through the use of a pensieve and collected memories. One memory is incomplete however, and Harry is tasked with trying to retrieve it from Professor Slughorn. After one unsuccessful attempt, Harry drinks his Felix Felicis, which he had earned earlier from Slughorn. Harry retrieves the memory, and he and Dumbledore learn that Voldemort has created 6 Horcruxes, and split his soul into 7 pieces to preserve his immortality.
Dumbledore tracks down the location of one of the Horcruxes, and he and Harry go to retrieve it. They travel to a cave, and Dumbledore drinks a potion from a cauldron to retrieve what appears to be the Horcrux. The two return to Hogwarts, but when they were gone Malfoy had let the Death Eaters into the castle vis the room of requirement. Dumbledore is cornered and killed by Snape, fulfilling his unbreakable vow. The Death Eaters then flee, while Harry chases after them and attempts to duel Snape. Harry then learns that Snape was the Half Blood Prince. The next day, Harry opens the locket, and discovers that it is not a Horcrux. The real Horcrux was taken by a R.A.B earlier.
On the current generation consoles, the game play mostly involves one of 3 minigames. There is a potion brewing game, where the player must brew a potion as quickly as possible. There is also an on-rails flying game, where the player flies through a series of rings. The third minigame is a dueling game. The player casts spells on the right stick and tries to take away all of their opponents health. There is also an open world, which serves as a connection between cutscenes and minigames. There are also collectible Hogwarts Crests hidden throughout the world which unlock extra characters in the multiplayer dueling.
The Wii release is very similar to the Xbox/PS3 releases, except that the right stick motions are replaced with motion controls for the spell casting.