World number one Andy Murray and Djokovic are in action later on Thursday.
However, Murray cut a frustrated figure as he was swept aside by the 20-year-old Croatian for the second time in the pairs four meetings. He lost to Goffin in the quarterfinals in Monte Carlo, his first clay tournament of the season.
"Most things weren't working particularly well".
"I didn't help myself find a way into the match to start playing better".
Sharapova's current ranking of 258, after a return from a 15-month doping suspension, was too low to merit a direct entry for the event and the organisers were looking to give her one of the four available wildcards, the report said. "He was by far the better player".
He will play the quarterfinal against Dominic Thiem of Austria, who won a thriller against Grigor Dimitrov of Bulgaria 4-6, 6-4, 7-6 (9).
That set hung in the balance until Djokovic was able to claim what proved to be the decisive break in the 11th game of the set and he was then able to serve out to progress into third round.
Djokovic had his playing time diminished this year because of an elbow injury.
The two players served up a treat for an expectant crowd following a delayed start due to rain and Djokovic had to be patient, with Lopez raising his game in his homeland. Lopez, apparently thinking Djokovic was challenging the prior shot, stopped play and lost the point to face set point.
"I can not promise to play or pull out right now".
It was Djokovic, who had dominated on the clay a year ago as he went on to win the Roland Garros title.
Canada's Milos Raonic was also successful today as he saw off Gilles Muller of Luxembourg 6-4, 6-4 while Kei Nishikori of Japan was forced to come from a set down to see of Diego Schwartzman of Argentina 1-6, 6-0, 6-4.
The player, who is now ranked 49th in the world, outplayed Murray, who has been in poor form of late and only recently lost in the semi-finals in the Godo Tournament in Barcelona. He withdrew from Barcelona last month because of a right wrist injury.
Nadal picked up his tour-leading 31st victory this year by easily defeating 16th-seeded Kyrgios, who never threatened after losing the first set.
"I haven't played bad, I played really bad", Nadal said. I think I have some margin to do it even better tomorrow and step forward.
Rafael Nadal and Novak Djokovic are set to face off in the Men's singles semi-final of 2017 Madrid Open on Saturday, which will also be their 50th career meeting.
On the other side of the draw Uruguayan Pablo Cuevas advanced to his first ever Masters series semi-final by outlasting German wonder kid Alexander Zverev 3-6, 6-0, 6-4.
In the women's Madrid Open, third seed Simona Halep remains on course to defend her title as she thrashed American Coco Vandeweghe 6-1, 6-1.
Halep will play Anastasija Sevastova of Latvia, who defeated Kiki Bertens of the Netherlands 6-3, 6-3.