Microsoft said on Wednesday the game had beaten movie releases such as Spider-Man 3 and book launches such as Harry Potter and the Deathly Hallows in opening sales.
Halo 3 represents the conclusion of a trilogy of games featuring the futuristic soldier Master Chief and his battle to save mankind from an alien coalition known as the Covenant.
The game has been praised for the scope of its action sequences and its engaging cinematic storyline.
Microsoft said more than 1m Xbox Live members had come online to take part in multiplayer games on the first day, making it the most active day in the online service's history.
"The initial demand we've seen for Halo 3 has been astounding and the game is on track to become the number-one gaming title of all time," said Jill Hamburger, vice-president of movies and games at Best Buy, the retail chain.
This is bound to push more people towards purchasing an Xbox 360. If Sony doesn't find a blockbuster game for its Playstation 3 console soon, it's going to be a long, cold winter for them.