Many people think the term "southpaw" came from baseball, but it can be seen in a letter in a Philadelphia newspaper of 1813:

"'Luk here mon, and convince yourself,' said he, holding up the Tickler, in the right paw, between the ceiling and the floor, and with the south paw pointing to the 'bow, vow, vow'."

It seems "south" refers to the opposite of what is considered "normal", or the right hand.