Flying into Germany - Best to fly to Frankfurt and then on to Berlin? or straight to Berlin?

Take a look at Skyscanner for flights to compare.
I always try to fly non stop from the west coast. I don’t sleep well on planes unless I fly business class. Even then I don’t sleep much. It’s a long haul and having to stay awake in an airport In the middle of the night CA time while waiting for a connection is not pleasant.

Check prices at someplace like Matrix ITA.
For Lufthansa, either Frankfurt or Munich are the connecting airports, both about the same price. Looking in May, lowest prices seem to be on Aer Lingus from LAX connecting in Dublin. There are no direct flights to Berlin from CA.

Adding to the advice to use ITA Matrix to find the best fares, keep in mind that if you do choose one of the few existing non-stop USA-Berlin flights, you'll have no same-day alternative in the event of a disruption (mechanical problem, bad weather, strike, etc.). USA-Frankfurt gives you the most options, with USA-Munich second.

If you decide to fly Lufthansa, they have a great Rail&Fly offer. For a flat fee, you receive a ticket valid on any same-day German train (including ICE high-speed trains) to your destination. You might have to call Lufthansa to arrange this; I've never had any luck booking Rail&Fly online from the US (but that might just be me!).

Check Icelandair. There will be a connection thru Iceland but it goes fairly fast. Good prices usually.

Your least expensive and a simple way is to fly Norwegian Air Shuttle from SFO or LAX to Gatwick. There you can catch EasyJet to virtually anywhere in Europe really cheap.
Berlin TXL doesn't have flights to the U.S. except one Delta JFK flight that's seasonal.

You don't compare prices with a list of company names. You use one of the many online aggregation sites that scrape the entire internet for information. You don't have to buy the ticket there if you are worried about a third-party company you've never heard of. But it tells you which airlines to investigate further, for THOSE dates and times. See our host's advice:

https://www.ricksteves.com/travel-tips/transportation

Definitely consider train from Frankfurt Airport to Berlin as well. It may be possible to do so using the above-mentioned Lufthansa Rail & Fly deal, in which case you will be protected if your flight is delayed and you miss the train.

In addition to the good advice you have already been given, I would also recommend to avoid transfers in the US, at least on the way back. Such a connection would mean picking up your luggage, going through customs, then checking in your luggage again. That is not the case if you transfer elsewhere.

You don´t even need to bother about getting to Berlin. The best/most interesting places (Rhine and Mosel valley, Bavarian Alps, Black Forst and Bodensee) are closer to Frankfurt anyway.

We don't have many details about your trip, but there is always the option of a "Multi-city" ticket -- fly into one city and fly out of another, which eliminates back-tracking to get back to the place where you started. This generally is comparable in price to a round trip ticket.

You don´t even need to bother about getting to Berlin. The best/most
interesting places (Rhine and Mosel valley, Bavarian Alps, Black Forst
and Bodensee) are closer to Frankfurt anyway.

I've been to all, and all are great. But Berlin is the place to which I keep returning.

Thank you everyone! I do need to go to Berlin to join a group I'll be traveling through Germany with. Sounds like flying to Frankfurt will offer more options. I"ll have to research how far/ how much time it takes on train Frankfurt to Berlin. And don't worry, I'll be seeing great areas of Germany, ending with my traveling companions in Munich, then I'll be in the Alps a few days on my own. I am looking forward to it all! Thanks again!

My trip to Germany is cancelled. Hoping to be able to go in 2022. Hope you're all doing fine.

Just because its the biggest doesnt mean its the cheapest, Ive flown into bought and my flight to Berlin was cheaper

What do you plan to visit?
If you are planning to visit the Rhineland in western Germany, yes, go to Frankfurt.

If you are focusing on Berlin, that's were your flight should go. Same with Munich.

And they are promising that the new BER airport will be open this fall.

As you can tell from the replies, you probably will not find a non-stop to Berlin. Tegel Airport cam't handle the traffic (at least before the shutdowns) and the new international airport is most of a decade late so I wouldn't bet on an opening this year. New airports are prone to notoriously difficult break-in periods anyhow. The suggestion of a multi-destination itinerary, bought as a complete ticket through a web function rather than assembling bits and pieces, can often save both time and money. Many connections are made through Munich as well as Frankfurt or you could find yourself connecting at London Heathrow (I'd prefer either of the German airports to Heathrow). I use a site like Matrix to do that research for you. PS: I've enjoyed visiting Berlin twice.

Coming back from Berlin this January we flew via Zurich to SFO (Swiss Air using United miles)

Margaret, I hope it works out for you in 2022!