Taking the bus is the cheapest way to travel from Florence to Milan. Buses traveling from Florence to Milan depart from either Florence's Autostazione Busitalia-Sita Nord or Piazzale Montelungo bus station and take at least 3:15 h to arrive at either Milan's Autostazione Lampugnano or Rogoredo bus station. Over 20 buses travel from Florence to Milan every day, with the first departing Florence at 2:10 a.m. Bus companies that travel from Milan to Florence include Flixbus, Baltour, and BusCenter. Ridesharing services like BlaBlaCar also frequently travel from Florence to Milan.

Taking the train is the fastest way to travel from Florence to Milan. Trains traveling from Florence to Milan depart from either either Florence's Santa Maria Novella, Rifredi, or Campo di Marte train station and take approximately 1:40 h to arrive at Milan's Centrale or Porta Garibaldi train station. Approximately 50 trains travel from Florence to Milan every day, with the first departing Florence at 6:53 a.m. There is also a much slower night train that travels from Florence to Milan, departing Florence at 1:47 a.m. and arriving at Milan at 7:12 a.m. Both Trenitalia and Italo travel frequently from Florence to Milan.

Taking the train is the most popular way to travel from Florence to Milan. Taking a train is at least 1:20 h faster than traveling from Florence to Milan by bus while only costing €16 more on average. High-speed trains traveling from Florence to Milan tend to be more expensive making taking the bus an attractive option for travelers looking to save money while traveling. Florence and Milan are located too close together to make flying an efficient way to travel.