Milan to Lake Como (Varenna)

With both, you would have to get to Milano Centrale first, then take the train to Lake Como. However, in terms of distance, LIN is much closer to Milano Centrale than MXP. At MXP, you would spend an additional 30 minutes on the train just getting to the train station. After that, from Milano Centrale to Varenna, it's about 2+ hours, depending on the train.

I don't know that this is a reason to go with one airport over the other, but if the prices were both the same, you'd save a bit of time flying into LIN.

But perhaps you can get a non-stop to MXP from USA. If transferring in another European city, then fly into LIN.

LIN is served by metro line #4 that does NOT go to Milano Centrale.

Buses, shuttles and cabs will take you from LIN to Milano Centrale in less than 30 minutes; the downside is that Buses, shuttles and cabs stop outside the Centrale station, not inside the tracks area like the train from MXP does.

Only takes a little over an hour from Milan to get a Varenna. Just take the direct train which runs quite often. But it only runs from Milan central.

I'll add that you can download the Trenord app (the local train company in Lombardia) and just buy the tickets at the time on the app for both the train from MXP to Milan and from Milan to Varenna. It would require you to have data although there is wifi in the Milano Centrale train station and at the airport.

As others have said LIN is closer but MXP is better connected to Milano Central train station so it is easier as an option to the train station.

I will just ask if you are sure you want to navigate a hour into the train station and then getting tickets for Varenna and then another hour to Varenna after your flight. Maybe you are better after a long flight than i am, but it sounds like a lot to plan on doing.
Also be aware of what time your flight gets into MXP, add an hour (plus time for tickets and immigration control) and then check the trains that are available to get into Varenna. They run hourly up until 9:20pm or so, but if you get into Milan after 6:30pm or so you're cutting it kind of close.

Milan is not my favorite city but having dinner there, seeing some of the city then spending the night there and getting on the train the next day is not a bad plan. This also allows you to deal with getting an Italian SIM card at the station, getting euros and any other 'getting into country' issues in the big city rather than in tiny Varenna.

My $.02, have a great trip,
=Tod

so another option over the train is a private taxi - a little more cost but will take you directly to whichever airport you choose without having to change trains or buses. Bellagio Taxi is a great service which we have used a few times.