It was only the second time PSV had conceded six goals at home in the Eredivisie and there was little warning of events to come at half-time with the score at 1-1, Vitesse having taken the lead through Lucas Piazon before the hosts equalised through Memphis Depay.
Mike Havenaar and Kelvin Leerdam gave the visitors a 3-1 lead with 15 minutes remaining before Karim Rekik pulled one back with six minutes to go.
Two goals from Davy Propper sandwiched Patrick van Aanholt's strike as Vitesse sealed their fifth successive win in style.
Two points behind Peter Bosz's side in second are Ajax, who kept a sixth clean sheet in their past nine Eredivisie home games. Davy Klaassen was the hero for the hosts against NAC Breda with two first-half goals before completing his hat-trick in the 64th minute.
The hosts equalised nine minutes into the second half through Sander Duits' penalty before they saw Damiano Schet sent off for a second bookable offence with seven minutes to go.
