World number one Novak Djokovic kicked off his title defence with a 6-3, 6-4 win over Dominic Thiem, while Andy Murray did his hopes of grabbing a spot at the season-ending ATP World Tour Finals no harm with an assured 7-5, 6-2 win over Jerzy Janowicz.
Nadal has been diagnosed with appendicitis which will require surgery, and while the world number two tried to play through the pain, he was clearly not at his best.
The Spaniard, who could lose his number two ranking to Roger Federer, looked out of sorts as the first set passed him by, but he gave himself a jolt in the second and looked well placed to level the match.
However, Lopez fought back with the same kind of aggression he had been showing in the first set and forced it to a tiebreaker before closing out the match with a terrific volley at the net.
With five spots still up for grabs at the season-ender in London, Australian Open champion Wawrinka, who fell at the first hurdle in Tokyo last week, suffered the same fate in China with a 5-7, 7-5, 6-4 defeat to Frenchman Gilles Simon.
"Two weeks I didn't win matches," said the Swiss on the ATP's official website. "But you have to accept that and see what the problem was.
“I think I'm playing okay. I just had two really bad matches. I will take the positives from losing early."
American Jack Sock produced another upset when he defeated Japan's Kei Nishikori 7-6 (7/5), 6-4. It was the American's first win over a top 10 opponent and brought Nishikori's hot streak to an end.
The Japanese came into the tournament after wins in Kuala Lumpur and Tokyo.
Djokovic not taking anything for granted
Djokovic, who is undefeated in 26 matches in China, had too much class for up-and-coming Austrian Thiem, winning 76% of his service points and saving both break points he faced.
"I had to be on alert from the start because he was serving already 215kph in the first service game," said Djokovic.
"He was serving big, playing big. He was going for it. I don't blame him. He's a young player, playing on center court; it's his opportunity to shine."
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