With your american licence is fine.
All major car rental companies do have offices in Santiago as in other major cities in CHile. Budget, Hetz, Avis, Eropcar etc.
I've had very good experiences with Europcar and United Car Rental
both are Chilean, good service, and pretty new cars.
what parts of the lake district are you interested in going to?
some places have unpaved roads and it might be wise to get something with a bit more grit
-:- Message from TripAdvisor staff -:-
This topic has been closed to new posts due to inactivity. We hope you'll join the conversation by posting to an open topic or starting a new one.
To review the TripAdvisor Forums Posting Guidelines, please follow this link: http://www.tripadvisor.com/pages/forums_posting_guidelines.html
We remove posts that do not follow our posting guidelines, and we reserve the right to remove any post for any reason.