The Katusha rider proved the strongest on the brutal climb that finished the mountainous 151km stage, holding off Samuel Sanchez (Euskaltel) and Sergio Luis Henao (Sky) to claim the win, and with it the lead in the general classification.
The 18 per cent gradient in the final climb proved no challenge to Rodriguez, who soloed away with an explosive surge to beat stage four winner Sanchez by nine seconds. Henao was a further three seconds back.
"It was a really hard final part, but very suitable to my characteristics," said Rodriguez.
"First I was able to slipstream Schleck, then Poels, then I managed to pass him and win. I couldn't win this stage if my teammates didn't work like they did. They did an incredible job both yesterday and today, so I have to thank each one."
The win gives Rodriguez a nine-second lead in the overall standings from Sanchez, with Christopher Horner (RadioShack) third some 21 seconds off the lead.
"I'm happy I have the leader's jersey for the second year in a row, now we have to do all we could to keep it. It won't be easy because of Saturday's ITT," continued Rodriguez.
"Races against the clock are not my speciality, but this one will be quite technical, with many ups and downs. It won't be a classic time trial and moreover now I have a nice gap so I think I have some chances, at least, to be on the podium in the final general classification."