Imagine Route 66 before development—hell, before pavement—and you'll begin to understand the iconic and oddly pristine nature of Argentina's Ruta 40 (or La Cuarenta, as it's locally known). In its entirety, Ruta 40 stretches from the Bolivian border all the way down to the continent's little toe, in Cabo Vírgenes—3,100-plus miles of gorgeous, unpredictable road-tripping that bounces past 18 rivers and 20 national parks, including the Moab-like Calchaqui Valley (home to the ancient ruins of Quilmes) and Talampaya, sometimes called Argentina's Grand Canyon. Drive it all, or follow the 1,200-mile, weeklong slice I did with a couple of friends a few years back in a rented VW Gol we picked up in the colonial city of Salta. The road skirts the Andes for miles on end, so impromptu jags led us to hikes and trout-filled streams. Often there'll be nothing for hours, and then the reward of a mirage proves real: the mystically lush valley town of Barreal or the petroglyphs at Talampaya National Park. Do not miss Posada San Eduardo, a charming, modest estate owned by a former Formula One driver in Barreal (Av. San Martín at Los Enamorados; no phone or website) and La Palmera restaurant, home to the best chivito (roast baby goat) on earth (Ruta 15 at Ruta 40, Villa Union, near Talampaya National Park, no phone or website). Near the finish line, allow for a couple of days in the fecund region around Mendoza, where—I can happily report—you'll find wines delicious and cheap enough to bring any road trip to a sudden, gluttonous end.