On September 7, 1960, Eddie Machen stepped into the ring to face the feared Sonny Liston.  To many, Liston was the “Uncrowned Heavyweight Champion” and a bout with Patterson was being called for by the fans and press alike.  Only Eddie stood in Sonny’s way.  The bout took place in Seattle and Eddie gave the brutish Liston all he could handle.  In the end, Sonny took a unanimous decision despite losing three points for low blows.

"Liston is a good fighter," Machen said, "but he won't knock down any walls. I don't like to alibi, but I hurt my shoulder six days ago in training and couldn't use my right too well. I want very much to fight him again when I have two hands." Liston, the number one contender for the crown, was equally unimpressed with second-rated Eddie. "All Machen wanted to do was go 12 rounds," he said. "He didn't want to fight. I had a bad night." Liston, who at 211 had a 15-pound weight advantage over Machen.

Machen later said he believed that Liston's handlers made deliberate use of illegal medication in an attempt to temporarily blind him during the fight. He theorized that Liston's handlers rubbed medication on their fighter's shoulders, which was transferred to Machen's forehead during clinches and dripped into his eyes. "I thought my eyes would burn out of my head, and Liston seemed to know it would happen," Machen said. When Liston fought Muhammad Ali—then Cassius Clay—in 1964, Ali returned to his corner after the fourth round and complained that there was something burning in his eyes and he could not see. "The same thing happened to me when I fought Liston," Machen said two days after Ali upset Liston. "Clay did the worst thing when he started screaming and let Liston know it had worked," Machen added. "Clay panicked. I didn't do that. I'm more of a seasoned pro, and I hid it from Liston."