[4] Born in Kapellen, Van der Poel comes from a family of professional cyclists; his brother David was also prominent in cyclo-cross racing, winning the 2013 National Under-23 Championships in Hilvarenbeek.

The following winter, Van der Poel advanced to the junior ranks, and was immediately dominant in this season; out of all the races he contested, he failed to finish first on only four occasions.

[15] Picking up where he left off the previous winter, Van der Poel's 2012–13 cyclo-cross campaign was flawless; he contested thirty races, and won every single one of them.

[27] In the lead up to the World Championships, Van der Poel dominated the Grand Prix Rüebliland event, as he won the opening three of the race's four stages.

Van der Poel finished 50th out of the 84 riders to complete the course, over two minutes down on the eventual world champion Igor Decraene of Belgium.

[30] In the road race, Van der Poel attacked on the final lap,[31] and bridged up to the race leader Franck Bonnamour of France; he later distanced him on the final climb of Via Salviati – around 5 km (3.1 mi) from the finish – and soloed away to win the gold medal,[6] ahead of Pedersen and Albania's Nikaj Iltjan.

[34] In his first race in the class, Van der Poel won the GP Mario De Clercq – in the BPost Bank Trophy – at Ronse, defeating nearest rival Gianni Vermeersch by twelve seconds.

[38] He completed a clean sweep of victories in the major cyclo-cross competitions, by winning at Ruddervoorde in the Superprestige the following day, leading home his rivals by almost a minute.

[39] He won a silver medal at the UEC European Cyclo-cross Championships in Mladá Boleslav in the Czech Republic,[40] finishing 23 seconds behind winner Michael Vanthourenhout.

Van der Poel turned professional with the BKCP–Powerplus team at the start of the 2014 season, joining brother David at the squad, having signed a four-year contract.

[48] He achieved his first professional victory at the Boels Classic Internationale Cyclo-cross in Heerlen, beating closest rivals Thijs van Amerongen and Rob Peeters.

At the 2018 European Cycling Championships in Glasgow, Van der Poel competed in the cross-country mountain bike and the road race, winning a silver medal in the latter.

He attacked from a leading group of three riders, including Alex Kirsch of Luxembourg and Trek–Segafredo and Estonian Mihkel Räim of Israel Cycling Academy, and rode over eight kilometers solo to the finish.

[52] At the 2019 Amstel Gold Race, van der Poel was the first of the favourites to attack at 43 km to the finish together with Gorka Izagirre, but their attempt was brought back by the peloton soon after.

Due to persistent back problems, worsened by his Olympic crash, Van der Poel did not defend his title at the 2021 Tour of Britain.

[58] He put an initial hold on his cyclocross season due to his continued back pain, and eventually raced twice before pulling out altogether.

[64] After a fourth in Amstel Gold Race[65] and a ninth in Paris–Roubaix,[66] Van der Poel made his first appearance at the Giro d'Italia,[67] the second Grand Tour participation of his career.

[71] He followed this up with two further wins and two silver medals before taking part in the UCI Cyclo-cross World Championships, which he won for a fifth time after a tight sprint against Wout van Aert.

[80] In October, Van der Poel won the UCI Gravel World Championships, dropping breakaway companion Florian Vermeersch with 13 km to go and winning solo with over a minute gap.