Greipel beat Australian stars Robbie McEwen and Graeme Brown at the end of a hot and windy 149.5km fourth stage from the Adelaide suburb of Norwood to the south-eastern coastal town of Goolwa.
Greipel, the 2008 Tour champion, has now won three of the four stages.
Lance Armstrong went clear with team-mate Tomas Vaitkous in a bold move near the finish, but despite building a lead of around 15 seconds they were caught well before the finish.
The windy conditions played havoc with the race and Spanish star Alejandro Valverde was among the riders who lost touch with the lead group before the finish.
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Australian Cadel Evans managed to stay with the front group as Greipel's HTC Columbia team worked brilliantly at the front of the race.
As always, the race will be decided by Saturday's second-last stage, which features two climbs of the tough Willunga Hill.
