Littler, 17, had stunned the darts world by beating Van Gerwen to win his first PDC senior title at the Bahrain Masters last week - his debut on the World Series stage - but the Dutchman was not to be denied on home soil.
The final was a tense affair, with both players exchanging breaks early on. However, Van Gerwen eventually pulled ahead and took out 85 in the deciding leg to seal victory.
It is the first time Van Gerwen has won his home Masters event.
Littler, despite the defeat, was still able to take some positives from the match. He averaged 106.71 throughout, higher than Van Gerwen's 100.59.
But Van Gerwen was ruthless in the checkouts, notching up an impressive 66.7 average on finishes.
For Littler, who won a repeat of the World Championship final against Luke Humphries 6-5 en route to the final at Den Bosch, it was further evidence at how far the teenage sensation has come in such a short space of time.
Speaking to ITV after the match, Littler said: "It went leg by leg, hold by hold. At the end when I hit a 180, he came back with one.
"Throughout the game, it was unbelievable. I put him under pressure or tried to - he just wouldn't miss.
"The crowd have been amazing, they want Michael to win and I get that."
Home favourite Van Gerwen was full of praise for his young counterpart: "Luke Littler will have a bright future ahead of him, we all know that. His scoring power is immense.
"He doesn't care about anything and he does his own thing.
"I needed my best performance. To win this trophy and win against Luke Littler in front of the home crowd is amazing."
