From Tucson, head east towards El Paso on I-10 to exit 281 (Hwy 83, South to Patagonia/Sonoita)
Take Hwy 83 all the way to the Sonoita Crossroads. (It will be the only stop sign you will encounter).
Turn right (west) on Hwy 82. Take Hwy 82 into Patagonia.
Turn left (south) on Third Avenue and right (west) on Duquesne Ave.
The Duquesne House will be on the left (south), halfway between Third Avenue and Fourth Avenue.