The world No 2 was due to face fellow Spaniard Lopez on Wednesday but felt a sharp pain during his final training session on Tuesday.
That pain was in the same leg injury that forced him out of the Australian Open last month and, following discussions with his medical team, decided to withdraw.
Nadal said: ”Doctors have told me that it is impossible to play, regardless of whether it hurts.
“There is a significant risk of increasing the injury and I have no choice.
“I was well prepared to play and I had hopes of doing something important here.
“I had done all the right steps to get well prepared for the tournament, which was my goal and my dream.
“Unfortunately, yesterday’s final training session before debuting again noticed a puncture in the same area where I had the problem in Australia.
“Doctors have told me that it is impossible to play, regardless of whether it hurts… There is a significant risk of increasing the injury and I have no choice.
“I was well prepared to play and I had hopes of doing something important here.”
Nadal has not competed since retiring against Croatia’s Marin Cilic in Melbourne last month.
He was in Acapulco hoping to close the gap on world No 1 Roger Federer.
Nadal added: “I still don’t know what it is, because we don’t know. It seems it’s not as bad as what I had at the Australian Open.
“Now my main goal is to find out the extent of the injury.”