The left-hander was cheered on by friend and compatriot 22-time Grand Slam champion Rafa Nadal (37) during his 6-3 7-5 victory over Max Purcell (25).
Lopez, who reached a career high ranking of 12 and holds the record for appearing in 79 successive Grand Slam main draws, will face Australian Jordan Thompson (29) on Wednesday.
"It's a really special win for me, probably one of the most special wins of my career so far, to be honest," Lopez, who has more than 500 ATP singles wins, said on court at the Santa Ponsa Country Club after his win.
"This is over my expectations, to be winning a match at this stage of my career in Mallorca, this beautiful place, surrounded by the ones that I love, my friends."
Nadal, who is currently out of action as he tries to recover from injuries, was joined by Carlos Moya in the stands to cheer on their former Davis Cup compatriot.
"Most of them came for my hypothetical last match. Luckily, it wasn't the last match of my life. I have another opportunity tomorrow, and this is very overwhelming, I have to say," Lopez added after only his second ATP Tour win this year.
