The world number two Nadal, coming off three lop-sided victories, encountered much stiffer resistance from his Davis Cup team mate, a fellow left-hander whose chipping and charging to the net had the Mallorcan repeatedly on the back-foot at Rod Laver Arena.
Nadal came to Melbourne Park under an injury cloud and had his left foot strapped by a physiotherapist early in the first set but moved nimbly enough to wear 30-year-old Lopez in the heat and seal the match in less than two and a half hours.
Nadal, the 2009 winner, advanced to his sixth consecutive quarter-final at Melbourne Park, where he will face either Czech seventh seed Tomas Berdych or another Spaniard in Nicolas Almagro.