Lake Como to Lake Maggiore transfer

The main train lines run north-south in that area because of the lakes. You could put together a route connecting Varenna on the east side of Como with Stresa on the west side of Maggiore using ferries and buses, but it would take several connections and lots of time. The train through MIlan is the fastest, cheapest, and simplest.

If you're going to have to do something non-direct anyway, I have a suggestion to offer: Include the Centovalli train trip in your route. The Centovalli train line runs from Locarno to Domodossala. It looks (from the Deutsche Bahn website) as if the trip will take at least 6-3/4 hours and require 4 transfers, but you will see nice scenery.

Looking at the regional rail map of Lombardy, you could take a train to Lecco, then change to a train to Como S. Giovanni, then a train to Mendrisio, then a train to Gallarate, then a train to Stresa. By the time you've done all that, you will have wished you would have just taken the train to Milano Centrale, then changed to a train to Stresa.

Main rail lines with direct trains generally pass through major cities and towns because that way they can serve more passengers. I don’t think there are many people interested in going directly from Varenna to Stresa on a daily basis, but there are tens of thousands who commute daily between the towns near lake Como and Milan, or between the towns near Lake Maggiore and Milan (and viceversa).
Incidentally even if you drove a car, the route would not still be very direct as the freeways also pass around the Milan metro area (due also to geographical obstacles).

As the others have mentioned, the quickest and most direct route between Varenna and Stresa is via Milano Centrale. The trip from Varenna to Milan is 1H:03M and from Milan to Stresa is a bit more than an hour (depending on which train you choose). Minimizing transportation times between destinations will allow more time for sightseeing.

Yes, it is a V-shaped route via Milan. A straight line route would involve crossing both lakes, or a circuitous route around the top of Lake Maggiore, and still crossing Lake Como. A mixture of boats and buses and/or trains.
Even with a car you still need to cross the lakes (ferries), or looping to the south (click here for map).

If you want to explore the lakes region, the circuitous driving route around the north end of Lake Maggiore could be fun.

I’ve been studying the route for our drive in the opposite direction. For you, a ferry across Lake Como to Menaggio, then along the entire shore of Lake Lugano then north to Locarno at the top of Lake Maggiore. Not fast but probably extremely scenic. We may go that way (in reverse) if we cross Simplon Pass but more likely we’ll go over Gotthard Pass (via the road tunnel unless it melts really early. :)

Enjoy the planning and the trip!

Thanks for the info. I'd love to rent a car and really explore around the lakes, but I'm not sure we have the time. Will have to check our schedule again.

If you are looking to rent a car in Varenna and drop it in Stresa then you are out of luck. The local car rental shop in Varenna is just that - local. You would probably have to go to Lecco to find a rental agency that would have the ability for you to just drop the car in Stresa.

Driving would be a little short and marginally faster. Train through Milan is the way to go.

Using a rental car comes with a few "caveats". Each driver listed on the rental form will require the compulsory International Driver's Permit, which is used in conjunction with your home D.L. You'll also have to be extremely vigilant to avoid the ZTL (limited traffic) zones that exist in many Italian cities. Hefty fines for each pass through these.