Milan to Zurich by train

First choice would definitely be Bernina Express. Don't overnight in Chur (nothing much to be seen there), but in St. Moritz instead, then head on to Zurich.

Second or ex aequo is Milano - Bellinzona - Locarno - Centovalli - Domodossola - Brig - Lötschberg - Berne - Zurich.

The Gotthard route (most direct one) is the least scenic. But I agree, Bellinzona with its castles is scenic. So is Arth-Goldau - but only if you made your way up to Rigi by cog railway which then would require a night en route.

I second a_p. The direct Gothard route is the less scenic one, but it can be upgraded with some detours, like:
Milan Porta Garibaldi dp by train 9.00 - Stresa ar 10.26, dp by boat (not daily) 11.15 - Locarno ar 14.30, dp by train 15.45 - Lucerne ar 18.41
or
Milan Centrale dp by train 7.35 - Capolago ar 8.45, dp by cog train 9.20 - Monte Generoso (view point, 1600m above sea level) ar 9.55, dp 11.45 - Capolago ar 12.27, dp by train 12.45 - Bellinzona ar 13.30, dp 14.06 - Flüelen ar 15.41, dp by boat 16.00 - Lucerne ar 18.41
Trains Lucerne - Zurich airport about every 30 min from 5.28 until 22.35; 1 1/4 hrs ride.

Milano - Zurich via Bernina - Albula (9 1/2 hrs trip, highly recommended):
Milano Centrale dp 6.20, 8.20, 10.20, 12.20, 14.20. Change at Tirano, Pontresina, Samedan and Chur, except for the Milan dp 10.20 train: direct panoramic Bernina Express train from Tirano up to Chur.
Optimal solution:
Milano Nord dp by train 8.59 - Como Lago ar 9.55, dp by boat 10.30 - Bellano ar 13.00, dp by train 13.33 - Tirano 14.50/15.40 - Bernina - St. Moritz ar 18.08. Next day: St. Moritz dp 5.57 - Zurich airport ar 9.46 (trains every hour).

The route via Brig is scenic too (along Lake Maggiore and Lake Thun). It would be a very good solution with a side trip from Brig to either Aletsch Glacier or Zermatt:
Milan Centrale dp 7.28 or 8.28 - Brig ar 9.16 or 10.16 - Riederalp (Aletsch) ar 9.50 or 10.50, resp Zermatt ar 10.52 or 11.52
Brig - Zurich airport: direct trains (2 1/2 hrs trip) at least every hour from 5.47 until 19.49

How about something that neither neckervd nor I thought about before - something unusual but for sure very scenic:

Milano - Lugano by train. From here, take the Palm Express (postal coach) along Lake Lugano and Lake Como and over Maloya pass to St. Moritz. Simply spectacular! Overnight. Then head on via either Julier pass (again by postal coach) to Chur and by train to Zurich. Or as above, by train from St. Moritz via Albula pass to Chur and Zurich.

The ultimate over-the-Alps tour (takes some planning): Milano - Bellinzona - Airolo by train. Now by postal coach via Lukmanier pass to Ulrichen in the canton of Valais. Overnight. Now by train (via Furka tunnel) to Andermatt. From there via cog railway down the narrow gorge to Göschenen. Now by train on to Zurich. Or something at least as spectacular: Ulrichen - Gletsch by train, now on via Grimsel pass (postal coach) to Meringen, then by train via Brünig pass to Lucerne and on to Zurich.

The choice is all yours...

And you probably thought you asked a relatively simple question Nakrob. LOL

As you can see the possibilities are numerous. Any of those suggested will be scenic, so you might want to look at them and consider which best fits your budget.

Asking how to get from MIlan to Zurich is like asking which chocolate you want out of a box of chocolates.

neckervd: I agree with you. That is why posters should say when they are intending to travel.

BTW: We forgot the route Milano - Bellinzona - Biasca - Lukmanier pass - Disentis/Mustér - Chur - Zurich. Or Milano - Bellinzona - San Bernardino pass - Thusis - Davos - Landquart - Zurich. Or from Thusis via Lenzerheide to Chur and on to Zurich. Or Milano via Paris to Zurich... ;-)

Why not bus Milano - Courmayeur - Chamonix - Geneva airport - ZRH, with the alternative Courmayeur La Palud - Chamonix via Punta Hellbronner?

neckervd: :-) Before we go any further (you forgot to mention Milano - Aosta - Grand Saint Bernard - Martigny - Bex - Les Diablerets - Zweisimmen - Spiez - Bern - Zurich) I suggest to wait for Nakrob's reaction. She/he might call us insane otherwise ;-)

Wow! I posted this from home last night and have just checked the responses from my office this morning. So much additional information!

I should have mentioned that this is a late June trip. We can leave Milan early on a Wednesday morning and then depart from Zurich airport at 18:00 on the Thursday. I also realise that my question was very open ended so appreciate the varied responses. I will have to wait until tonight to digest all the above posts! Any further posts in the next 12 hours appreciated.

We defiantely want to go by train rather than coach, I think I saw a reference to a ferry which would be good.

How would you work in a ferry on Lago Maggiore connecting with train or bus in Ascona, one of my favourite small towns in Switzerland, neckervd and a_p? The walk from the dock to the bus station is not far even with luggage and from there you can go to Locarno train station.

Coming in to Ascona on a ferry is about as picture postcard as it gets and totally changes a traveller's image of Switzerland. The palm trees just boggle the mind somehow.