Van der Poel first opened a gap while van Aert was on the floor after a fall, but his 40km solo run for the line was a powerful marker for the season ahead.
The Dutch rider crossed the line at Harelbeke stood up on his pedals with a military salute 1min 31sec ahead of second placed Jasper Stuyven whose fellow Belgian Van Aert was third a second behind.
The 207km race over 17 hills is the first of a series of races known to cycling fans as 'holy week' leading up to next Sunday's Tour of Flanders, run over many of the same roads.
Van der Poel attacked several times and was reeled in each time by Van Aert before the key moment.
Showers early in the race made the cobbles slick, and Van Aert fell at the foot of the Paterberg hill.
Van der Poel was merciless and set off with blistering pace on his solo bid.
While Van Aert gamely went in hot pursuit with a bloody elbow Van der Poel raced on past fan-packed roadsides in a relentless and unflinching manner.
Winner last season of the world championship in Glasgow, the Tour of Flanders and Paris-Roubaix, Van der Poel has established himself as the man to beat in the big one day challenges.
Van Aert was far from the only rider to fall on the narrow Flanders lanes as Bora's Emil Herzog was sent flying head first into a ditch.
The E3 was first staged in 1958 and named after one of the major highways which runs through the Flanders region.
Van Aert won the race in 2022 with a long-range attack from 42km out alongside teammate Christophe Laporte and retained it in 2023 after closing a gap on Tadej Pogacar and Van der Poel and crushing them in the sprint.
