Following up his debut triumph on the red dust on Monday in Munich, Murray denied Nadal a third straight triumph in the Spanish capital -- and record fifth overall -- and raised fresh doubts over the Spaniard's form heading into the French Open.
The Briton's strong performances this week suggest he may be a real contender in Paris, when holder Nadal, who has struggled for consistency since returning from injury and illness, will be bidding for a record-extending 10th Roland Garros crown.
"To play Rafa in Spain is extremely tough and this is the reason why we play tennis for these matches," Murray said after receiving the trophy from Spain's Queen Sofia.
"It's one of the toughest things in tennis to try to beat Rafa on clay," added the 27-year-old.
"I'll keep trying to play well over the next few weeks with Roland Garros just around the corner."
Murray had never beaten third-seeded Nadal on clay in six attempts but raced into a 3-0 lead at the futuristic magic box arena and fended off three break points to close out the set.
The world number three broke Nadal twice more to open a 4-0 lead in the second and finished him off on his first match point when the Mallorcan sent a weak forehand return into the net.
Nadal, 28, congratulated Murray for a "great season" and said he would try to keep working back to top form at this week's Rome Masters before heading to the French capital.
"Obviously, this wasn't the match I wanted or expected to play today," Nadal said.
"Although it's not nice to end it like this, it has been a very important week for me, very positive, in which I rediscovered sensations I had not had on a tennis court for a long time," he added.
It was Murray's 10th Masters crown and 33rd career title, while Nadal missed out on a record-extending 28th Masters and 66th title overall.
Nadal needed a win to stay fourth in the world rankings and he will drop to seven when they are updated, putting him outside the top five for the first time in a decade.