Madrid and Seville are 334 miles (537 km) apart, and the best way to make the trip is by a direct flight, which will take just about one hour.
If you don't mind an extra hour and a half of travel time, you can also take a high-speed train directly from the center of Madrid to the center of Seville.
After you explore Madrid and Seville, you can add two nights further north in Barcelona with this 7-day itinerary.
Duration: 1 hour
Flying is the quickest and most convenient way to get to Seville, and there are many direct flights from Madrid-Barajas Adolfo Suárez Airport (MAD) to Seville Airport (SVQ) each day. While smaller, budget airlines will charge for baggage, larger airlines like Iberia will include a personal item and a full-sized carry-on.
Duration: 2.5 hours
At Madrid's Atocha Train Station, there are many trains to Seville Santa Justa each day, and they depart every half hour. The main train company in Spain is Renfe, and its high-speed trains are called “Ave.” You can purchase tickets ahead of time online, via the Renfe app, or at the train station.
You may have the option to select a "flexible" fare, which allows you to modify your trip if you'd like to stop in other cities. Make sure to board the train at least ten minutes prior to departure in order to make sure you get a seat.