Dries Mertens scored his 14th goal 1, on Friday to move into first place in the Dutch Eredivisie.
Tim Matavz and Stanislav Manolev also scored for PSV, which could have climbed to the top of the standings last week but settled for a 1-1 draw with Utrecht. AZ Alkmaar can reclaim the lead Saturday with a win at Roda.
Matavz fired PSV into the lead just after the half-hour mark and Mertens added to the lead in the 76th. Mike Havenaar pulled a goal back after 84 minutes for Vitesse, but Manolev sealed PSV's win 3 minutes into stoppage time.
PSV won for the third time in its last four games to move two points ahead of AZ. Vitesse dropped its second straight and is 12 points off the pace.
Also Saturday, Heerenveen hosts Utrecht, NAC hosts De Graafschap, and Heracles hosts Excelsior. On Sunday, Feyenoord hosts Ajax, RKC Waalwijk hosts Venlo, NEC hosts Den Haag, and Twente hosts Groningen.