Transport from Venice to airport in ROME

It is strictly a matter or risk tolerance. What is the downside if you miss your return flight? You need to be at the airport by noon to 12.30 at the absolutely latest. The 7.37 train from Venice arrives Termini at 11 and hour, walk to, take a cab to the airport will get you there around the noon mark. The 6.18 will give you an extra hour of time. The high speed trains are generally on time but there can be exceptions. Every now and then there is a maintenance problems and the infamous Italian train strikes - frequently announced, seldom held. So strictly via time it could work but there is little margin for error (delay). So what is plan b? I personally would not do it.

If you are at Termini, the Leonardo Express is probably faster than a cab.

If YOU have a cast iron stomach, ice-water in your veins and a well stocked wallet, give your plan a try.

No way I would try to do it

Any possibility to re-arrange your trip so you end in Rome?

Weekday or weekend? bahn.com shows trains as early as 6.06 arriving Termini at 9.30. The only issue I'd have is if there's a last-minute delay . . . accident on the tracks, strike . . . there's no recourse that will get you to FCO in time.

The vaporetto runs all night, but on a limited schedule and doesn't make all the stops. You could take a water taxi.

If it is not a Sunday, there is actually a direct train to Fiumicino Aeroporto from Venezia Mestre at 5:37. You would have to take a connecting Regionale from Venezia S. Lucia at 5:15. The last "N" boat arrives at Ferovia (S. Lucia station) at 4:47 am, so that would work.
For later trains from S. Lucia, the regular No 1 boat will be running.

I'm in the camp with the others who say nay.

Venice is definitely not where I'd want to be the morning of a flight from Fiumicino, even if it doesn't depart until mid-afternoon. The risk of something going awry and missing the plane is just high enough for this lady (who has experienced an Italian train strike). If it were me, I'd stay the last night in Rome where you're not as dependent on trains from Venice running like clockwork or running at all.

Regarding the fear of strikes, they do not affect the high-speed freccia trains, only the slower regionale. The earliest train would be your best bet. Can a delay happen? Certainly. In dozens of train trips while we lived there we had one mechanical on a freccia that made us an hour late. Other delays were 5 to 20 minutes and infrequent.

As mentioned by Frank, depends on your tolerance for risk.

There's also the possibility of a vaporetto strike (my sister encountered one on her trip to Venice). Check while in Venice, and if one is planned, be sure to book a water taxi the night before, to take you to the train station.

As everyone else is saying, how lucky do you feel? I know I wouldn't enjoy my last day in Venice if I spent it worrying that everything was going to go fine - but it's your trip.

Any chance of a late-evening flight Venice to Rome, sleep near/at the Rome airport ? Then at least you could have the last day in Venice. Once you're asleep, one city looks like another.
Edit -- Trenitalia has a late-night train at 12:08 arriving Termini at 6:35. Sleep on the train.

Thanks to everyone for the responses. Very helpful. I hadn't realized the distance from Venice to Rome. We're going to just shift plans a bit so end up in Rome day before heading home. I don't have the stomach for the stress I'd probably feel that final morning, taking train to Rome for flight. Thanks again!

That is one of the reasons I often suggest buying a map and putting some pins in the map. This is also a good case for the open jaw ticketing - into Rome and home from Venice. Probably would have been cheap also. But I think you are smart not to try to do it in one day. There has been a lot of changes at the airport so I don't know the amount of time you would need to an afternoon flight.