The 29-year-old Russian disposed of Romanian Adrian Voinea 6-3, 6-0, in a light drizzle. On hardcourt or grass, that would have been enough for a stoppage. On clay, it only motivated Kafelnikov to play on.
The veteran last won two straight matches on the surface at the 2001 French Open when he reached the quarters of the Grand Slam he won in 1996.
This clay season began poorly for Kafelnikov with a 5-0 Davis Cup loss in Buenos Aires to Argentina. But Kafelnikov quickly made up ground once he landed in Europe and moved into action at the Estadio Nacional.
"I'm sorry that the match wasn't more difficult," said the winner. "But he was suffering more than I was. I knew with a 6-3, 4-0 lead that I would win the match. I wanted to stay out there even in the rain and finish."
Kafelnikov next plays Davis Cup teammate Nikolay Davydenko, who defeated German Alexander Waske 6-3, 7-6 (7-3).
Davydenko has made an accelerated recovery from a broken wrist suffered in Memphis two months ago.
"A doctor said I would be out for maybe two months, he said to think about coming back in May or June," Davydenko said. "But I went five days or a week without playing at all, then I tried to practice with just the forehand for three weeks, no backhands because I play with two hands. I played three days before Miami and now I've been playing two weeks with both hands on the backhand, so now it's no problem."
Max Mirnyi of Belarus was another seeded player to advance in a toournament where the top three seeds made exits each of the first three days.
The 25-year-old Mirnyi, who won his first career title in February in Rotterdam, rode an 11-ace performance to a 3-6, 6-3, 6-4 victory over Romanian qualifier Victor Hanescu.
The seventh-seeded Mirnyi took a 5-4 lead in the third set and served out on his second match point after his 21-year-old opponent saved the first.
"I'm playing much better than last year, I feel like I'm a better player," said Mirnyi. "My game can be tough to handle. But winning my first tournament has given me a lot of confidence. I believe in my abilities a lot more."
On Friday, Mirnyi will face Spain's Feliciano Lopez, who defeated Portyugal's Bernardo Mota, 6-3, 6-4 in a second-round contest.
Mota, a 31-year-old part-timer who earned his last ATP victory six years ago, had become the first Portuguese to player to reach the second round on the clay of the Estadio Nacional since Nuno Marques four years ago.
But Mota was quickly brought down to earth by Lopez, who had beaten second-seeded Australian Open finalist Rainer Schuettler in the opening round.
Women's top seed Katarina Srebotnik was upset by German qualifier Julia Schruff, 6-4, 3-6, 6-3.
Second-seeded defending champion Magui Serna of Spain beat Hungarian Petra Mandula to move into the last eight while France's Stephanie Cohen-Aloro defeated Lopez' girlfriend, Maria Sanchez Lorenzo, 6-4, 2-6, 6-2.