Varenna Italy to Wengen Switzerland by train

Easiest is train to Milan, then an EC train Spiez, then train to Interlaken Ost, Lauterbrunnen, and Wengen. You only have to pay for the portion in Italy if you have a Swiss travel pass.
Edit - Actually as far as Domodossola, Italy.

You don't need to know the "travel crossover" in advance. Just go to the Swiss Railways site ( https://www.sbb.ch/en/ ), feed in Varenna to Wengen, with a date and time and it will give you the quickest route.
The Swiss site has Italian trains loaded, so this works. The Italian site (Trenitalia) does not have Swiss trains loaded.

The crossover point between the two railway companies, and the point at which your Swiss Pass becomes valid on this route is Domodossola. You can see that on the Swiss Pass map here: https://www.sbb.ch/content/dam/sbb/de/pdf/freizeit-ferien/ferien-kurztrips-schweiz/internationale-gaeste/uebersichtskarte_synoptic_map_2017_low.pdf
You will need to get an Italian ticket from Varenna to Domodossola. You do not need to get off the train in Domodossola.

we had this exact question about 3 weeks ago but I can't find it.

the best route is not to get a direct EC train to from Milan to Spiez, that's the fastest route for people who don't want to see the scenery because it goes through the new tunnel.

assuming that you aren't travelling half way around the world to see the inside of a tunnel, use the same route as far as Brig (this also increases the number of trains available from Milan), it may be that the train calls at Spiez and Bern/Basel, or it may be going to Geneva but get off at Brig. Then take the regional train via Kandersteg, this uses the original route and has the views. Takes about 1 hour longer but is worth it.

And as said, since you have a SwissPass just buy a ticket from Varenna to Domodossola via Milan.

Thank you very much. I purchased tickets from Varenna to Domodossola as suggested but I see that I am supposed to purchase reservations (mandatory) for the short leg from Domodossola to Brig. I have not had any luck completing this on a couple of different occasions. It gives the locations but then says NA and I have tried several dates and the same response came up? Obviously I am doing something wrong?

I purchased tickets from Varenna to Domodossola as suggested but I see that I am supposed to purchase reservations (mandatory) for the short leg from Domodossola to Brig.

lawiseman, the leg from Varenna to Milan is a regional train, and no reservation is possible.
Your ticket from Milan to Domodossola wil be for a specific train and should list train number, date, time, vehicle and set number on it, i.e. you already have a reservation.
After Domodossola Swiss rules apply, your Swiss pass is valid and no reservation is needed. You (usually) don't change trains in Domodossola, you stay sitting in the same seat. After Domodossola the Swiss ticket inspector will come round and want to see your Swiss Pass + ID (passport).
Where are you seeing that reservations are mandatory from Domodossola to Brig?

Seems to be a quirk in the SBB route planner. If you put in Domodossola to Wengen using an EC train, it will show the "R" in a box indicating reservation required. If you then try to purchase that ticket, it will give you an error message. It will only allow you to purchase connections that do not involve an EC train.

I'm Chris F, if you already have a ticket on an EC train, the seat reservation is included. There is no "R" in a box for the same EC train when you look at Brig to Wengen.

I bet the Swiss system is being literal. Although Domodossola is the crew change point (from FS Trenitalia to BLS wearing SBB uniforms) and the ticketing crossover point too, Domodossola is still in the country of Italy and the tracks will be in Italy until the actual political border. And the rule is that on EC trains, everything above Regionale Veloce, in Italy reservations are mandatory. I'm guessing that they are being pedantic that reservations are required for that short stretch still in Italy, and by extension to the next stop.

Maybe right, maybe wrong..... In any event, la wise man, you're already in the seat you've had all along so just stay there. No reservations required on that train in Switzerland, the same as none required in Switzerland for French TGV trains although they are required for the same seats once they cross into France.

R in the notes line with FA and restaurant symbol means reservations available