Born to Mexican-immigrant Serapio Huerta and his Texas-born wife Margarita Garza, Fender made his first radio appearance at age 10 on Harlingen's KGBS-AM radio station KGBT, when he sang a current hit, "Paloma Querida".In 1959, Fender recorded the blues ballad "Wasted Days and Wasted Nights". The song was a hit, but he was beset by legal troubles in May 1960 after he and a band member were arrested for possession of marijuana in Baton Rouge, Louisiana. After serving nearly three years in theAngola prison farm, he was released through the intercession of then Governor Jimmie Davis, also a songwriter and musician. Freddy Fender underwent a kidney transplant in 2002 donated by his daughter and a transplant of the liver in 2004. Nonetheless, his condition continued to worsen. He was suffering from an "incurable cancer" in which he had tumors on his lungs. On December 31, 2005, Fender performed his last concert and resumed chemotherapy.
He died in 2006 at the age of 69 of lung cancer at his home in Corpus Christi, Texas, with his family at his bedside. He was buried in his hometown of San Benito.