Origin of "What's up?"

[aldiboronti]

That source above does not address the origin of the phrase at all, simply the Bugs Bunny version, What’s up, doc. (And ‘outlived Bugs Bunny’? He’s dead?)

Here’s the real nitty-gritty from OED.

up, adv. 2

11 d. colloq. Occurring (as a special, unusual, or undesirable event); taking place, going on; amiss, wrong. (Very freq. from c 1850.)

1838 MRS. GASKELL Let. 19 Aug. (1966) 37, I did not mention a word to Lucy but she must have guessed something was ‘up’. 1849 ALB. SMITH Pottleton Legacy ix. 75 He saw something was ‘up’. 1851 MAYHEW Lond. Labour I. 21 A shout in answer from the other asks, ‘What’s up?’ 1908 Times 29 May 15/6 We constantly thought that something was going to be up.

e. Amiss or wrong with a person, etc.

1887 RIDER HAGGARD Jess vii, There’s something up with that girl.

From this there is a natural development to mean ‘what’s happening, what’s going on’.