From the north (Milan, Florence), the best exit for Perugia on the A1 motorway at Valdichiana, where the superstrada SS75bis branches into Umbria at Lake Trasimene and continues towards Perugia.

From the south (Rome) travelling northwards along the A1 motorway the best exit for reaching Perugia is at Orte, which is connected to the regional capital at first by the ss204 to Terni and then by the E45 (or SS3bis) from Terni to Perugia, at Ponte San Giovanni, take the SS75bis from  to Perugia.

The A14 motorway down the Adriatic coast of Italy has an exit at Cesena for the E45 "superstrada" to Città di Castello, at Ponte San Giovanni, take the SS75bis from  to Perugia.

The SS75bis has five exits for Perugia (from North): Perugia-Ferro di Cavallo, Perugia-Madonna Alta (best to reach the "Renato Curi" football stadium) , Perugia-San Faustino (best to reach the main railway FS station, also good for the old town center), Perugia-Prepo (good to reach the old town center) and Perugia-Piscille (best to reach the Ideal Hotel).