The fourth-seeded Moya, the Buenos Aires champion in 2003 and 2006, lost to 108th-ranked Argentine qualifier Maximo Gonzalez 6-4, 6-4. Gonzalez led 4-0 in the first set and almost blew a 5-1 lead in the second.
"Without a doubt, it's the most important win of my career," Gonzalez said.
Moya, also a finalist in 2004, blamed his loss on leg pain he's been suffering for more than a year.
"I haven't competed in a month," he said. "Now the priority is to put myself in good physical condition."
Gaudio, the hometown winner in 2005, had a better reason. He lost to Daniel Gimeno-Traver of Spain 6-2, 4-6, 6-2 in his first match on tour in a year because of injuries.
It's been 21 months since the Argentine won a match on the tour and he made a fighting start with breaks in each set, spoiled by 11 double faults.
Oscar Hernandez, who lost to Almagro in the second round here last year, defeated Spanish compatriot Almagro 6-2, 1-6, 6-3. Martin Vassallo Arguello was one of four Argentine winners on the day, topping Montanes 6-2, 6-3, and Pablo Cuevas of Uruguay ousted Schwank 6-3, 6-7 (4), 6-0.
Third-seeded Tommy Robredo, last week's winner of the Brazil Open, defeated Potito Starace of Italy 5-7, 6-3, 6-3, but Thomaz Bellucci, who lost his first ATP final last week to Robredo, was beaten by seventh-seeded Marcel Granollers of Spain 7-5, 7-5.
Juan Monaco, the 2007 champion, routed Argentine wild card Sergio Roitman 6-0, 6-0, and fifth-seeded Jose Acasuso, who has reached at least the quarterfinals six times since his 2001 debut, beat Spanish qualifier Daniel Munoz-De La Nava, 6-2, 7-6 (4),
Other winners included Diego Junqueira of Argentina, Fabio Fognini of Italy, and qualifier Franco Ferreiro of Brazil.