1. To throw into a state of confusion: The unexpected news in the paper discombobulated Stephanie and she was not sure how to respond.
2. To confuse or to disconcert; to upset; to frustrate: The politician was completely discombobulated by the critics in the audience.
3. Etymology: from 1834, American English, a fanciful coinage of a type popular then (originally discombobricate).

Possibly an alteration of or a play on the words discompose, discomposure, etc., "a loss of the ability to remain calm and self-assured; especially, under difficult or emotional circumstances".