FC Groningen saw off ADO Den Haag 1-0 in the highest-profile of Tuesday night's KNVB Beker third-round ties.
Michael De Leeuw scored the only goal in the 33rd minute as Groningen won the battle of the only two Eredivisie sides in action.
Third-tier amateurs ADO '20 stunned Eindhoven, from the division above, 6-1 at Sportpark de Vlotter in Heemskerk.
Two goals apiece from Benny Kleine and Franky Zinhagel and a Mark de Loor penalty saw the Topklasse minnows astonishingly take a 5-0 lead inside 13 minutes.
Serhat Koc pulled one back before half-time, but Jeffrey Mols had the final say just after the hour mark.
There was another upset win for a team from the third tier as Rijnsburgse Boys knocked out Eerste Divisie side Emmen 7-6 on penalties after a 0-0 draw.
Cambuur Leeuwarden were also victorious on penalties against Stormvogels Telstar in a meeting of two sides from the second tier.
Mark Diemers gave Cambuur the lead, but Jerge Hoefdraad equalised in the 90th minute.
Cambuur held firm throughout extra time, despite the dismissal of Tim Bakens, and they emerged victorious 4-3 from the spot.
Go Ahead Eagles won 3-0 away to De Graafschap in the evening's early kick-off in Doetinchem.
The goals all came before half-time, Joey Suk setting the visitors on their way in another all-Eerste Divisie clash before Quincy Promes and Khalid Karami made the result safe.
Lars Veldwijk's double saw Eerste Divisie side Dordrecht past underdogs Scheveningen 2-1.