World number three Murray had lost his last two matches on clay against Berdych, runner-up to Roger Federer in Madrid last year, and was beaten 7-6 6-4 by the Czech sixth seed after Nadal battled past Spanish compatriot David Ferrer 4-6 7-6 6-0.
Second seed Federer, making his return after a seven-week rest, was knocked out in the third round by Japan's Kei Nishikori on Thursday, two days after a shock reverse for world number one and top seed Novak Djokovic against Grigor Dimitrov.
The heavyweight quartet of Djokovic, Federer, Murray and Nadal have won 26 straight tournaments going back to Rome 2010 when all four have featured in the draw.
Chasing a fourth title since coming back from a knee injury in February, Nadal will meet Pablo Andujar in Saturday's semi-finals after his countryman - a wild card ranked 113 in the world - upset 14th-seeded Nishikori in the quarter-final.
Big-hitting Berdych, who is yet to win a title in 2013, will take on 15th seed Stanislas Wawrinka for a place in Sunday's final after the Swiss beat seventh seed Jo-Wilfried Tsonga of France 6-2 6-7 6-4 in the late game.
"Even though I didn't start well I was able to turn the first set on my side, which was very important," Berdych told a news conference.
"You know, with him (Murray) it's never easy," added the 27-year-old. "Even though we played just two sets they were really long. You really have to fight a lot for a small chance."
Murray, 25, battled through a gruelling three-hour encounter against Frenchman Gilles Simon on Thursday that finished after one o'clock in the morning local time (2300 GMT) and the Scot appeared increasingly weary as Friday's match wore on.
He said he was frustrated not to have taken more than two of his nine chances to break Berdych's serve and that he was suffering from a sore hip at the start.
"I did play a very long match yesterday and finished extremely late so I was a bit stiffer probably than usual at the beginning but once I warmed up it felt better," he added.
"The Spaniards like starting late so you've just got to deal with it."