Van Nistelrooy was playing in his first competitive match for the Netherlands since last year's World Cup.
The Netherlands moved into the second place in Group G, three points behind Romania, who beat Belarus 3-1. Bulgaria dropped to third.
Portugal were held to their second straight qualifying draw, this time 2-2 with visiting Poland.
Jacek Krzynowek scored the final goal for Poland in the 88th minute. Mariusz Lewandowski also scored for Poland, while Maniche and Cristiano Ronaldo scored for the hosts.
Poland lead Group A with 20 points, two more than Finland, who were held to a 0-0 draw by Serbia. Portugal are third with 16 points, one more than Serbia.
Northern Ireland, who had been a surprise in qualifying after beating both Spain and Sweden in Group F, lost 1-0 to Latvia.
Sweden, who were held to a 0-0 draw by visiting Denmark, lead Group F with 19 points, three more than Northern Ireland and Spain.
The other results on Saturday were: Georgia 1, Ukraine 1; Hungary 1, Bosnia-Herzegovina 0; Luxembourg 0, Slovenia 3; Moldova 0, Norway 1; and Slovakia 2, Ireland 2.
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