Holmes was born in Jamestown, Texas, and was raised on his family's farm. And he went to school in Burkeville, Texas Holmes played college football at Texas Southern University.
Holmes was selected by Pittsburgh Steelers in the eighth round of the 1971 NFL Draft. He was part of the legendary Steel Curtain defense along with fellow linemen Joe Greene, Dwight White, and L. C. Greenwood. While quarterback sacks were not an official NFL statistic until 1982, the Steelers credit Holmes with a career total of 40, eighth on the franchise's all-time list. This includes team-high totals of 11 in 1974 (including a stretch of six consecutive games with a sack, which ties him with Greene and Greg Lloyd for the longest such streak in team history) and 10.5 in 1975.
He was intensely fierce on the playing field and was often characterized as the most feared man on the Steelers defense.
Holmes played six seasons with the Steelers before being traded due to on-going weight problems in 1978 to the Tampa Bay Buccaneers, where he failed to make the team coming out of preseason. He played three games for the New England Patriots in 1978 before retiring.
Holmes' number 63 was later issued to All-Pro center Dermontti Dawson. The number has since been taken out of circulation as being "unofficially retired" in honor of Dawson, who would be inducted into the Pro Football Hall of Fame in 2012.
In the off-season preceding the 1973 season, Holmes had an emotional breakdown while driving on the Ohio Turnpike, firing shots at a police helicopter as it pursued him. On March 16, 1973, he was charged in the shooting of a Highway Patrol Heli-pilot. He was found in a field near his abandoned car in Goshen Township, Mahoning County, Ohio. When apprehended, he threw his gun away and put his hands up. He was given five years' probation. Diagnosed with acute paranoid psychosis, he was believed to be depressed and having marital troubles.
Until his death, Holmes lived in Texas on a ranch near Wiergate, a small town with a population of 461 found near the Louisiana border, where he had his own church and was an ordained minister. He was also a wrestler, and actor. In 1986, Holmes appeared in WrestleMania 2 and made other appearances as a professional wrestler. He appeared in an episode of "The A-Team" in the 1980s.
Holmes died in a one-car accident near Beaumont, Texas on the night of January 17, 2008. He was driving alone when his car left the road and rolled several times, about 80 miles (130 km) from Houston, according to a Texas Department of Public Safety dispatcher. Holmes was thrown from his car and was pronounced dead at the scene, according to the Texas Department of Transportation. He had not been wearing a seat belt.
Holmes was buried at the Pine Hill Cemetery in Jamestown, Texas.