The distance from Florence to Amalfi is about 340 miles (550 kilometers)—a long trip best started early in the morning, regardless of what means of travel you opt for.
The most convenient way to get from Florence to Amalfi is by a combination of train and private transfer (4.5-5 hours). Replacing the private transfer with a ferry is another convenient option that is easily accessible during the summer season (5-5.5 hours), and an experiential, scenic change from road travel.
Driving all the way between Florence and Amalfi is costly, expensive and inconvenient but is doable if you are comfortable driving the hairpin turns and the heavy congestion once closer to the Amalfi coast (5.5 - 6 hours).
Make sure to check this 7-day Amalfi Coast itinerary that includes a sunset boat tour between Amalfi and Positano, as well as a day trip to Capri and Anacapri.
By Train and Private Transfer
Duration: 4.5 - 5 hours (more with stops and traffic)
This is the most convenient way to get from Florence to Amalfi. Take the high-speed train, run by both Italy's train operators Trenitalia and Italo, from Florence's train station Firenze Santa Maria Novella to Salerno (3 hours and 40 minutes).
Once you arrive in Salerno, arrange a private transfer for the remaining distance to get to Amalfi (1 hour).
Because direct trains between Florence and Salerno are not particularly frequent you can choose to swap out Salerno with Naples as the destination (3 hours), but keep in mind that the private transfer would be longer and therefore pricier with the switch.
By Train and Ferry
Duration: 5 - 5.5 hours
This is both a convenient and an affordable way to get from Florence to Amalfi.
Take Trenitalia or Italo's high-speed train to Salerno's train station. Once in Salerno, the walk from the train station to the port, Porto di Salerno, is less than 3 minutes. Both Travelmar and NLG run ferries between Salerno and Amalfi (40 minutes). Make sure to arrive on time as ferries are not particularly frequent during the day. Moreover, because the ride offers a panoramic view of the Amalfi coast, arriving even earlier gives you the chance to secure a seat on the top deck. In terms of comfort, Italian ferry services are known to be clean and prompt, and bar and toilet amenities are available on board.
Similar to the previous option, you can swap Salerno with Naples as both cities have ports with daily ferries to the town of Amalfi. Salerno is a favorable option as the distance between the Naples train station and its Molo Beverello port requires a taxi, whereas in Salerno the port is a very short walk from the station. If the Salerno train and ferry arrangement does not work with your schedule, you may decide to look into Naples.
Duration: 5.5 - 6 hours (more with stops and traffic)
This is the least convenient way to get from Florence to Amalfi. Besides the fact that the approximately 340-mile ride along the A1 is long (about 5.5. hours), the tolls are expensive, and once near the Amalfi coast driving conditions become difficult for inexperienced drivers. If you choose this option, it is recommended that you rent the car once outside Florence to avoid the ZTL zones (limited traffic areas) that are common across Florence's city center and where you may likely pick up a hefty fine or two. See this Florence city guide for more tips on navigating the city.
Potential stops along the way include Rome for cacio e pepe (more ideas in this Ultimate Guide to Rome), Naples, and Pompeii, though it is recommended that you make your way directly to Amalfi before sunset when driving those narrow hairpin turns becomes increasingly difficult.