San Francisco to Lyon - Plane to Lyon or Plane to Paris/Train?

You could check the schedules and if convenient, take the TGV from CDG to Lyon.

Not sure where you are only seeing multiple connections in order to get to and from Lyon. Google Flights shows many flights a day between San Francisco and Lyon with only a single connection. I have never heard of an airport with the CDF designation. I assume you mean CDG. There are direct flights to Paris in about 11 hours. But there are single connections that take 14 (ish) hours with an adequate connection time. That's only a 3 hour difference. And gets you into Lyon a lot earlier than spending a night in Paris and taking the train. Airlines can't legally book connecting flights that can't be reached in time. But if you want a bit of a cushion, then 2 hours. If you want a big fat cushion, then 3 hours. A lot depends on the airport and whether you need to change terminals.

Look at Delta or Air France. You can buy the whole itinerary. It’s Seattle to Amsterdam or CDG and then either a flight within Europe or a train ticket from the CDG train station to the Lyon train station included in the fare. One change,
There’s no reason to schlep yourself into Paris and loose a day.
My choice, and I do this at least once a year: check my suitcase but keep valuables with me, take the overseas flight, switch to the domestic flight, and I’m at my destination.

Flights from the West coast typically land early enough to just get a TGV to Lyon that same day, straight from the airport. Allow 3 hours between landing and departure. Better still: some airlines (AF and maybe others) offer connecting "flights" where the "flight" to Lyon is actually a TGV.

Else, AMS would be my choice of connecting hub, especially if you don't check luggage (my track record of luggage actually making tight connections in Amsterdam is poor).

Many thanks Balso, Elizabeth, Jean and Philip - appreciate the thoughts and the quick reply.
I've always thought it best to get to the destination in one go - connecting flights included and think it probably wise to do that to Lyon... it can be a bit nerve racking figuring out the best routing (go though AMS, CDG, LHR, etc.) and scheduling. It sort of makes sense to go AF to CDG and then a connecting AF flight to Lyon. Think you are right not to spend a night in Paris just for the sake of travel convenience. Was there for 5 days in February (it was FABULOUS) and I really wish to see Lyon, Avignon, Dijon.

Sure wish there was a non-stop to Lyon, but it's not to be. That should be the worst of life's problems. ;)

Happy travels.

I used to travel to and from Lyon on business from the west coast of the U.S. repeatedly, before moving to Lyon.

I did both -- fly to Paris followed by TGV directly from CDG to Part Dieu (no need to go to Gare de Lyon -- that's an unnecessary step); or fly to CDG, AMS, or FRA and take a connecting flight to LYS, which then necessitated either a taxi ride or RhônExpress tram into central Lyon.

Either is fine. Flights from the west coast to CDG tend to land pretty early in the morning so catching a TGV for the two hour trip to Part Dieu was pretty easy.

I tended to do the flight/TGV combo when I had more time or when it was a longer visit, and the connecting flight to LYS option when it was a shorter trip. Not sure why you're finding so many connections. It should be simpler than that.

have done SFO - Frankfurt/Munich - Lyon a number of times on United and Lufthansa. Pretty straightforward, usually schedule to have 2-3 hours for the connection. Personally we've always preferred flying to Lyon rather than the Paris train strategy - it's a much smaller airport to get through, the luggage comes out faster, etc.