If FedEx and Amazon set up private airports dedicated to these machines, only put cargo in them, and make their flight routes distinct from other aircraft, I imagine this could be up and running faster than people think. Edge cases shouldn’t result in loss of life, so getting through regulations and insuring should be much easier than other situations.
Don't forget that aircraft falls on someone or someone's property.
Takeoff and landing are the tricky parts.
(I say this as someone who’s firmly on the skeptical side of the spectrum regarding the near-term prospects for fully autonomous vehicle control.)