Zurich to Lake Como

The way you laid out your itinerary, you will be doubling back. Do Zurich -> Luzern -> Mürren -> Lake Como.

If you're a regular reader of this Forum, you may already know the following. But just in case:

You will need an International Drivers Permit for Italy (in addition to your US license). You get this at an AAA office (cheaper for members, but open to all).

You will pay a hefty premium if you rent your car in Switzerland and return it in Italy. However, the insurance cost can be much lower on Swiss rentals, so you may still come out ahead.

I assume you're also aware that you won't be driving to Mürren. You'll have to leave the car either in Lauterbrunnen or Stechelberg, and pay for parking.

And you can't use the car to get round Zürich either. Best to pick it up when you are leaving Zürich.
Zürich --> Mürren --> Luzern --> Como is the quickest route, as the north-south Autobahn goes via Luzern, Gotthard tunnel to Como. Going South from Mürren / Lauterbrunnen involves a slow (but spectacular) route over the top of the Alps (Grimselpass etc.).

If I decided to go Lauterbrunnen to Lake Como, is the slow drive through the Alps safe (Grimelpass) ?

Can you explain what you mean by safe? Are you worried about robbers on the road?

I've never seen robbers on any road. But don't pick up strangers.

The Grimselpass, as all the other high mountain passes, takes more concentration to drive than does an Autobahn. These pass roads are a series of 180° hairpin bends up to the pass and down the other side.
It is spectacular for the passengers (so long as they have no problems with heights), but the driver sees a lot less as he/she has to concentrate on the road.
For example look at this video: https://www.youtube.com/watch?v=_cG_jCe4qwI
Or this one: https://www.youtube.com/watch?v=MRCyZNQ_f_s

Is this what you meant by "safe".

By safe I mean do the roads have barriers, are the roads well marked? We have driven in Ireland around the ring of kerry and slea head drive- does anyone know how driving through the Alps compares?

Always well marked, barriers if needed, it is as safe as your driving and that of others on the road at the same time make it.

It takes plenty of concentration.

caforman8188,
Look at the two videos I posted ( https://www.youtube.com/watch?v=_cG_jCe4qwI and https://www.youtube.com/watch?v=MRCyZNQ_f_s especially the second one).
Alpine pass roads have barriers on the bends. On the straights it is a line of granite pillars at the end of the road. The road is good quality. As Nigel says, it needs concentration, which means the driver does not get to appreciate the views, but the passengers do.

Thank you for your advice. The videos are very helpful. So I am thinking of going right from renting car at Zurich airport, driving to Lucerne-stay 1 night, then driving to Lauterbrunnen-stay 2 nights. Sad to not see Zurich, but would rather have the time in the Alps...