The Italian Yamaha rider finished in 42 minutes 14.611 seconds, beating his team mate Jorge Lorenzo by more than five seconds and Australian Ducati rider Casey Stoner by more than 23 seconds.
Rossi now leads the standings after seven of the season's 17 races with 131 points, with Lorenzo at number two on 126 and Stoner third with 122.
The three men were tied at the top with 106 before the Dutch race.
"It's fantastic because this track is special and there is a lot of history. My father won this race in the 250cc (category)," the 30-year-old Rossi told Dutch TV station RTL7.
"It's great when you can ride your 100th victory," he added after unrolling a 10-metre wide poster showing his 99 previous grand prix wins.
In the 250cc category, Japan's Hiroshi Aoyama won to take the lead in the world championship from Spaniard Alvaro Bautista, who fell in the penultimate round and did not finish after hitting the back of Aoyama's motorbike.
Spain's Sergio Gadea won the 125cc category, beating his compatriot Julian Simon by almost a second.
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