Frank De Boer is still waiting for his first win in charge of Holland after his side were forced to come from behind to claim a 1-1 draw against Italy in Nations League Group A1.
Van De Beek's leveller less than 10 minutes later was his country's first goal in 326 minutes, extending their winless streak under manager De Boer to three matches.
The striker already had five goals to his name this season, which kicked off on September 18, and carried his form onto the international stage, with Karol Linetty scoring in between the Bayern Munich player's double.
In a repeat of the 2018 World Cup final, France ran out 2-1 winners against Croatia in Group A3.
Antoine Griezmann gave France an early eighth-minute lead, which was cancelled out by Nikola Vlasic, before Kylian Mbappe's winner with just over 10 minutes left.
Liverpool forward Diogo Jota scored twice after Bernardo Silva opened the scoring as Portugal beat Sweden 3-0 to go level with France at the top of the group.
Romelu Lukaku netted twice in the first half, including a penalty to restore the lead after Birkir Mar Saervarsson's leveller.
Three days on from a hard-fought comeback to beat Belgium to briefly move top of their group, Gareth Southgate's side stumbled to a first defeat on home soil since September 2018.
Scotland fought and scraped their way to an eighth game unbeaten with a 1-0 win over the Czech Republic at Hampden Park following Ryan Fraser's goal, while also in Group B2, Israel claimed all three points in a 3-2 win in Slovakia.
Jonny Williams' first international goal gave Wales a 1-0 win over Bulgaria in Sofia.
Wales went back to the top of Group B4 with 10 points from four games, while elsewhere Fredrik Jensen returned to haunt the Republic of Ireland as he fired Finland to a 1-0 victory in Helsinki.
Northern Ireland's frustrations continued as a Stuart Dallas own goal condemned them to a 1-0 defeat to Norway in Oslo.
It was a seventh defeat in eight for Northern Ireland in this competition, keeping them bottom of Group B1.
In Group B3, Russia and Hungary played out a goalless draw while Turkey drew 2-2 with Serbia.
In Group C2, Estonia drew 1-1 with Armenia and Georgia were also held to the same scoreline by North Macedonia following Gjanni Alioski's last-gasp penalty.
Kosovo drew 0-0 in Greece in Group C3, while Slovenia stormed to a 4-0 victory in Moldova.
In C4, Belarus beat Kazakhstan 2-0 while Lithuania drew 0-0 with Albania.