Frederick missed the entire 2018 campaign due to Guillain-Barre Syndrome, an autoimmune disease that weakens muscles and attacks the nervous system. He returned to play a full 16-game season in 2019 and was named to the Pro Bowl.
"After much consideration, discussion, and reflection, I have decided to retire from football," Frederick wrote in a Twitter post on Monday.
"I started a journey almost two years ago that completely blindsided me. When I developed Guillain-Barre Syndrome, I did not know how to handle things. I was scared. That experience forced me to re-evaluate my life priorities."
Frederick added that facing the potential end of his career due to the illness forced him to imagine life after football - even as he put the uniform back on in 2019.
"I made my return to the field, played well overall, and was selected to the Pro Bowl, but it was a difficult year for me," he wrote. "Each day I faced a struggle: I could no longer perform at my highest level. Playing 'well' is not what I expect of myself and is not what my teammates deserve. Because of this, I know my days as a football player are done."
Overall, Frederick made five Pro Bowls and was named a first-team All-Pro once after being selected by Dallas in the first round of the 2013 draft.
"Travis Frederick, by the nature of his center position, was the core piece of what I believe to be one of the most talented and skilled NFL offensive lines that has been assembled," Cowboys owner Jerry Jones said in a statement on Monday. "His leadership ability, production, and intelligence put him at the top level of interior offensive linemen in our league for many years."
Fellow offensive lineman Joe Looney, who signed a one-year, $2.4-million contract to stay with the Cowboys this offseason, started in Frederick's place during 2018 and could fill the same role going forward.