Venice and Florence are two of the most popular cities to visit in Italy and, thankfully, are also connected by a fast and efficient rail service and highway known as the autostrada. The distance between Venice and Florence is about 258 kilometers or about 160 miles.
The route between the two cities is an interesting one, stopping by many Italian cities that are also worth visiting like Padua, Ferrara, and Bologna. If you only have a short amount of time in Italy, you can really focus on this route as these cities are good representations for the regions of Veneto, Emilia-Romagna, and Tuscany.
The train between Venice's Santa Lucia station and Florence's Firenze Santa Maria Novella Station takes a mere two hours and five minutes. If you factor in the train's city-center to city-center service, it is far more efficient than flying. Just make sure you book a hotel close to the train station, so you can get off, check-in, and be ready for your day of sightseeing.
Between renting a car, parking fees, and the cost of gas, driving between these two cities tends to be more expensive than one ticket on the train. It's usually only worth it if you are traveling in a large group or if you plan on making stops along the way that are not easy to reach by train. Driving between Venice and Florence typically takes about three hours on a day without much traffic.
If you're looking for something less expensive than a train ticket, the bus is also an option. However, the price difference is not so extreme and you will only be saving a couple of Euros. It's also a longer ride and can take up to five hours.