The Norwegian, who is the top seed, saw off his opponent 7-6 (7-2) 6-3 to set up a quarter-final clash with home hopeful Federico Coria, who defeated Dusan Lajovic 4-6 7-5 6-4.
Ruud was taking to the court for the first time since being in ATP Cup action in early January, with ankle injury ruling him out of the Australian Open.
But on the scene of his maiden ATP title win in 2020, Ruud – who has won five tournaments since – looked in good shape.
"I feel, obviously, very good in Buenos Aires. I was a bit nervous coming back because it's the first time I have to defend a title," he said.
"Everything is a bit different since two years ago. When I won here it was a surprise. I was young.
"[This] was a good start. First time playing on clay in six months, so everything is a bit new again.
"Of course, I prefer to play on clay, but it takes some time to get used to the court and playing points."
Third seed Lorenzo Sonego also advanced through to the last eight in straight sets, the Italian beating Sebastian Baez 6-3 6-3 to set up a meeting with Fernando Verdasco.
Unseeded Spaniard Verdasco, seeking an eighth career title, progressed thanks to a hard-fought 2-6 6-3 7-5 win over Thiago Monteiro.
At the Dallas Open, John Isner won his opening match on home soil with a 7-6 (7-1) 6-7 (7-9) 7-6 (7-5) victory over Kevin Anderson.
Isner will next take on either Vasek Pospisil or Jurij Rodionov, with the qualifiers scheduled to meet on Friday (AEDT).
Marcos Giron and Jordan Thompson are also in the quarter-finals after seeing off Liam Broady and Brandan Nakashima respectively.