Lopez was born on the Uintah and Ouray Indian Reservation in Fort Duchesne, Utah. His mother was a Ute Indian, and his father was a Juaneño.
Lopez attended Orem High School in Orem, Utah, where he chose boxing over football. He married as a teenager and moved to Pasadena, California, where he boxed out of the Pasadena YMCA. He later recalled that he learned to box from his father and added, "But sometimes I learned when I watched my father hit my mother."
Lopez became a popular boxer in Los Angeles during the late 1960s and early 1970s, fighting out of the Los Angeles Main Street Gym for much of his career. His brother, Danny "Little Red" Lopez, also went into boxing and became the world featherweight champion. Both of the Lopez brothers were managed by Howie Steindler.
Lopez was given the nickname "Indian Red" because of his flaming red hair and Native American heritage. In 1968, when Lopez became the first Native American boxer to be ranked as the No. 1 contender in any weight class, Pulitzer Prize winning sports writer Jim Murray wrote:
"I don't know how he is as a prize fighter, but Ernie (Indian Red) Lopez certainly is disappointing as an Indian. I mean, he doesn't look like something John Wayne would chase down the street shouting something about 'damned redskin.' 'Damned redhead,' maybe. But, Lordy, the skin is even freckled! Now, whoever heard of a red-headed, freckle-skinned Indian? ... 'What was your Indian name?' I asked Indian Red? 'Ernie,' he told me."
Lopez had a career record of 51-10-1, and fought bouts in England, Hawaii, Japan and Mexico. In 1967, Lopez wore an Indian chief's headdress into the ring in a match against Musahi Nakano in Japan. Lopez said, "I bought the thing at Disneyland to take over with me. ... I liked it so much I was going to keep it. But it turned out they have this custom in Japan where the fighters exchange gifts before the fight. Nakano gave me a samurai warrior's jacket and I gave him the headpiece."
Lopez's three bouts against Hedgemon Lewis in the late 1960s drew extensive media coverage. Going into the first fight in July 1968, Hedgemon Lewis was undefeated in 23 bouts, and both fighters were considered top contenders in the welterweight class. Lopez won the first bout in a ninth-round knockout, which the Los Angeles Times described as follows:
"Like Gen. Custer at Little Big Horn, Hedgemon Lewis got to wondering where all those Indians were coming from. And like his ancestors, Ernie (Indian Red) Lopez staged a fistic massacre Thursday night when he battered the previously unbeaten Lewis into a state of helplessness before a roaring turnaway mob of 10,400 at the Olympic Auditorium."
Lopez won two out of the three bouts with Lewis. In 2004, Lewis said of Lopez, "He was aggressive and always on the attack. Ernie was a crowd-pleaser because he was a fighter. Period. He fought." Actor Ryan O'Neal, who managed Lewis when Lewis fought Lopez, added, "Lopez was a warrior. He was also a gentleman, a decent man. But as a fighter, Lopez would hit the other guy so much he would become exhausted. Because of that, Lopez would always fill an arena, because he would give the fans their money's worth.... It was his heart that made him win." Another writer said of him, "He was an aggressive fighter who knew only one direction: forward."
On February 14, 1970, Lopez got a shot at the world welterweight boxing title in a bout against Cuban Jose "Mantequilla" Nápoles in front of a sellout crowd at The Forum in Inglewood, California. Lopez was knocked down in the 1st, 9th, and 15th rounds before the bout was called as a technical knockout in the 15th round. In 1971, boxing writer Dan Hafner said of Lopez:
"It is the misfortune of Ernie (Indian Red) Lopez to come along when one of the all-time greats, José Nápoles, rules the welterweight division. The fiery, part-Ute Indian demonstrated beyond doubt on Thursday night that he is the class of the rest of the 147-pounders. In his smartest and possibly best fight of his career, Lopez pounded out a unanimous, one-sided 10-round decision over highly regarded Oscar Albarado and gave a masterful performance."
Sugar Ray Leonard, who watched Nápoles fight Lopez, shared a similar opinion, "If it wasn't for Nápoles, Ernie probably would have been champion."
Lopez got a rematch against Nápoles, and a second shot at the title, three years later on February 28, 1973—again in front of a sellout crowd at The Forum. The second bout proved to be a turning point in Lopez's life. Lopez had reportedly won the first six rounds, and Nápoles had cuts above and below his eye and on the bridge of his nose. At the start of the seventh round, Nápoles hit Lopez squarely in the face, and Lopez fell to the canvas, where he lay unconscious for three minutes. After the knockout, Nápoles cradled Lopez's head and repeated, "Please wake up. Please wake up."
Reports indicate that Lopez's life went into a tailspin after the 1973 loss to Nápoles. He fought two more bouts and lost both in technical knockouts. He was divorced from his wife and took to a life of wandering. His brother, Danny Lopez, said, "It was the losses to Nápoles and the divorce that sent Ernie into a tailspin. He was a hurt man." Lopez's ex-wife also attributed the decline to the loss to Nápoles: "I think he lost confidence, his goal was destroyed. He was depressed and angry. We started having marital problems."
For twelve years from 1992 through 2004, Lopez was out of touch with his family and was considered a missing person. His ex-wife said, "The last time I saw him, he was kind of a street person. That was in 1992. He gave up all of his possessions and then went out in the world like a person wandering. It was really sad because he just gave up."
In early 2004, Lopez was selected for induction into the California Boxing Hall of Fame. With the impetus of the Hall of Fame induction ceremony, a police officer with the Los Angeles Police Department agreed to assist Lopez's family in trying to locate him. In February 2004, Lopez was discovered living in a homeless shelter in Fort Worth, Texas. When contacted by his ex-wife in 2004, Lopez stated, "I'm not lost. I'm right here." On learning of his selection for the Hall of Fame, Lopez told the Los Angeles Times, "Why are they doing this for me? I wasn't good enough for the Hall of Fame." Shortly thereafter, Lopez was re-united with his four children and 23 grandchildren.
Lopez's story became the subject of multiple newspaper and television stories, with reporters and television camera crews coming to the homeless shelter to interview him. He told the Los Angeles Times at the time that he did not recall why he moved to Fort Worth, but he recalled "living with a church family in Missouri, shoveling snow for a hotel owner in Portland, Maine, sleeping in New York's Central Park, working construction in Florida and cleaning hotel rooms in Phoenix." He told another reporter, "I've been all over the United States. Might have missed a few states, but it's sure a nice place. But I never stayed too long anywhere."
On October 3, 2009, Lopez died in Pleasant Grove, Utah from complications of dementia at age 64.