Zamudio made his professional boxing debut on August 13, 1987, defeating Jerome Wilson, 1-2 coming in, at the Great Western Forum in Inglewood, California, by a four round unanimous decision as part of the Paul Banke-Jesus Poll fight's undercard.
[4] After his first loss, Zamudio returned to the United States, where on August 26, he outpointed 1-4 Ramon Solis over ten rounds at the Aviation Gym in Redondo Beach, California.
[1] Zamudio then outpointed Rafael Morales on November 11, 1988 at Mexicali, before fighting Jose Manuel Diaz on April 4, 1989 at the Great Western Forum, once again, in Los Angeles, California.
After one more fight (a ten round decision win over Jorge Ortega),[6] Zamudio defended his regional title for the first time, meeting Martin Cardenas on June 28, 1989 at San Diego.
[7] Wins over Antonio Flores and Jose Luis Herrera followed the Cardenas victory and then Zamudio boxed Javier Diaz, a 63 bout veteran, at the Harrah's Hotel and Casino in Stateline, Nevada, for the vacant NABF Flyweight title, on April 12, 1990.
On June 29, 1996, Zamudio scored a third round knockout of former WBO world champion Jose Quirino at Fantasy Springs Casino in Indio, California, which made the WBC rank him among the top challengers on the flyweight division once again.
After two more wins, Zamudio travelled to Bangkok, Thailand, where he challenged the WBC's interim world flyweight champion Chatchai Sasakul, 28-1 coming into their bout, and lost by a twelve round unanimous decision at the Prince Palace Hotel, May 9, 1997.
Ysaias Zamudio then fought Alejandro Montiel for the WBC's Continental Americas' flyweight title on March 14, 1998 at Arizona Charlie's, in Las Vegas, Nevada.