The Lotto-Belisol rider, who won the first stage on Thursday in a mass sprint, held off Sky Procycling's Swift.
The riders set off at a rapid pace before Kevin van Melsen and Gediminas Kaupas broke away.
They were caught by an attack led by Andreas Kloden but in the final sprint Greipel reigned him in and crossed the line ahead of Swift.
"It may look simple to the people watching, but it's not," said Greipel. "The final was hard but in the end all went well."
Prologue winner Jimmy Engoulvent retains the yellow jersey.