The Dutchman was quick off the mark in the first minute, netting the fastest goal of the season at that point, to open the floodgates for a convincing win over a Saints side managed by former Red Gordon Strachan.
The victory may have only lifted United to fourth in the table but it was a sign that the striker was going to be worth every penny of the money invested in him, when completing his delayed arrival from PSV Eindhoven.
Van Nistelrooy doubled the lead in the 34th minute before Ole Gunnar Solskjaer got in on the act when converting a corner taken by Nicky Butt.