Although United dominated, they had to wait until the 40th minute to take the lead.
Derby keeper Stephen Bywater could only parry a Cristiano Ronaldo (in pic) shot which fell to Giggs who tapped in his landmark goal.
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Carlos Tevez scored two to put United 3-0 ahead before Steve Howard bagged Derby's first away goal of the season after 76 minutes.
Ronaldo completed the scoring with a last minute penalty for the home side.