Flight from Florence.....

There are no direct flights to Florence from the US, so at least one stopover is inevitable. Please provide more info - where is "home"? Cannot look up flight info without a destination city...

You don't say where you are flying to, but Rome or Milan would be a better option for direct flights to many North American cities. Of course, you'll want to weigh the time and cost of a train to one of those cities against the time and cost of a layover when flying out of Florence.

Home is Chicago - ORD

I don't mind one layover as direct seems too expensive.

From Venice, you can get to Toronto and Montreal non-stop on Air Transat.
Delta flies seasonally to Atlanta and JFK.
American flies seasonally to Philadelphia.
That's about it for non-stops from Venice.

You can fly non-stop from Rome FCO into ORD on Alitalia and United Airlines seasonally.
Now, you've just got to figure out what "Seasonal" means.

O'Hare is one of the great airports of the world. But it really doesn't serve Europe as well as some other airports in "the East."

Where is "Home"? You haven't filled out your profile, so I have no idea.
According to https://en.wikipedia.org/wiki/Florence_Airport you can fly from "Aeroporto di Firenze-Peretola" to: Düsseldorf, Amsterdam, Barcelona, Bucharest, Catania, Chișinău, Elba, Frankfurt, Geneva, London-City, London-Gatwick, London-Luton, Madrid, Munich, Palermo, Paris-Charles de Gaulle, Paris-Orly, Rome-Fiumicino, Tirana, Zürich, Seasonal: Brussels, Lyon, Olbia, Stuttgart, Vienna
Where do you want to fly to?

I just checked Google flights. Fly Florence to FCO to ORD on Alitalia. 13 hrs 10 minutes.

FLR only has European flights.
You can fly to ORD via the following hubs (each with at least 3 daily flights each direction):
via FCO (with Alitalia)
via CDG (with AirFrance)
via FRA or MUC (with Lufthansa)
via AMS (with KLM)
via ZRH (with Swiss)

FLR is also connected to DUS, MAD, VIE, BCN, LGW, but flights are limited to one a day, therefore not always suitable for connecting to the US through .

What is the exact date you are looking at?

Florence offers a bunch of one change flight. You can also look at Pisa. It's 45 minutes by train from Florence and a bigger airport. It offers one stop flights from there to ORD.

I wouldn't bother to go to PSA from Florence.
PSA has many choices in terms of European low cost airline flights (it's a RyanAir hub), however in terms of major traditional airlines, Florence offers more options.
The only additional option I"d like to mention is British Airways from Bologna (BLQ). BLQ has 3 daily pairs to London Heathrow (LHR) with BA, which is an American Airline partner. Bologna is a short 37 min train ride from Florence (plus you need about 20-25 min from the Bologna Centrale station to the Bologna airport on a bus or taxi).

Can fly British Air from Florence to LHR, then LHR to ORD either on British Air or American.

@ TXtwinmama:

......except that currently British Air does not fly from Florence to Heathrow (LHR).

Bologna is the closest option. Pisa has only one BA flight to LHR, but it's in the afternoon, therefore unsuitable to catch the connection from LHR to ORD on the same day. You will likely need to spend a night in London.

If you count connecting times, it may be easier/quicker/more efficient/cheaper to take the train from Firenze SMN to Roma, I think there may be direct trains to Roma FCO without changing trains.