It's basically a more boastful way of asking "Whats up?", it's like asking how someone is doing and saying you're in a good mood at the same time.
Popularized by Method Man in the N.A.S.A song "NASA Music" with E-40, another originator of slang.
Bobby: You man how are you doing?
Joey: Hey what's upper??!
Bobby: Damn why are you in such a good mood?
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What's popping my nigga? E-feezy style
What's uppers bitch, i'm a skeet all up on you
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As a kid everyone on always said what up and everyone one said the sky, so I came up with a cool wat o say what's up , my friends said whats up to me and I said (whats upper)Just a cool way to say Hello.Whats upper guys.
Someone walks up to ya Boy and said what up Tez - I'll reply (Whats upper)what you up to fam.