The Schalke striker netted with a close-range finish late in the first half as the Dutch maintained their 100% record with one game to go.
Bert van Marwijk's side had already qualified for next summer's tournament in Poland and Ukraine by being guaranteed at least the best runners-up spot, but they were clearly intent on keeping their winning run going.
Robin van Persie hit a post but the hosts had to be content with one goal.
Moldova have proved the toughest opponents for Holland in the group, with Huntelaar also scoring the only goal of the game in the reverse fixture 12 months ago.
Holland dominated possession in the first half without carving out too many clear-cut chances.
Kevin Strootman fired over before Van Persie met Erik Pieters' cross only to see his header punched away by goalkeeper Stanislav Namasco.
Dirk Kuyt also tested Namasco before the Liverpool forward created the opening goal in the 41st minute.
The 31-year-old played the ball in front the right and Huntelaar turned it home low from close range.
Gregory van der Wiel then fired high as the hosts continued to press.
The World Cup finalists showed no signs of taking their foot off the gas in the second half and Van Persie fired a shot against the post.
Van de Wiel's foul on Gheorghe Ovseanicov gave the visitors a free-kick on the left and Igor Bugaev headed Denis Zmeu's delivery over the top.
But that was the only scare for the home side as they made it nine wins out of nine in the group.