The US star goes up against the likes of Katy Perry, Bruno Mars and Justin Bieber at the annual awards show.
It all takes place at three venues across Northern Ireland's capital, with local band Snow Patrol playing a free gig to 15,000 people outside City Hall.
"The city is literally vibrating with joy," said frontman Gary Lightbody.
The singer, whose hits include Chasing Cars and Run, added: "It's kind of a dream to stop the traffic in Belfast.
"Very often Northern Ireland in the past has been in the news for other reasons and this is a really, really amazingly positive reason to be in the news."
Lady Gaga, 25, is up for the night's two biggest prizes, best song and best video - both for Born This Way, the title track of her current album.
In the best song category, she goes up against Bruno Mars's Grenade, Jennifer Lopez's On The Floor, Katy Perry's Firework and Adele's Rolling In The Deep.
Her competitors for best video include the Beastie Boys, whose star-studded short film for the single Make Some Noise features cameos from Steve Buscemi, Ted Danson, Elijah Wood, Chloe Sevigny and Kirsten Dunst.
Teen stars Justin Bieber and Selena Gomez are both performing at the event.
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