The star linebacker played for 20 NFL seasons with San Diego, Miami, and New England before retiring in 2009. He died of a self-inflicted shotgun wound.
He joins a list of several dozen football players who were found to have CTE. Boston University's center for study of the disease reported last month that 34 former pro players and nine who played only college football suffered from CTE.
"I was not surprised after learning a little about CTE that he had it," Seau's 23-year-old son Tyler said. "He did play so many years at that level. I was more just kind of angry I didn't do something more and have the awareness to help him more, and now it is too late.
"I don't think any of us were aware of the side effects that could be going on with head trauma until he passed away. We didn't know his behavior was from head trauma."
That behavior, according to Tyler Seau and Junior's ex-wife, Gina, included wild mood swings, irrationality, forgetfulness, insomnia, and depression.
The NFL faces lawsuits by thousands of former players who say the league withheld information on the harmful effects of concussions. According to an AP review of 175 lawsuits, 3,818 players have sued. At least 26 Hall of Famer members are among the players who have done so.
Seau is not the first former NFL player who killed himself, then was found to have CTE. Dave Duerson and Ray Easterling are the others.
"He emotionally detached himself and would kind of 'go away' for a little bit," Tyler Seau said. "And then the depression and things like that. It started to get progressively get worse."
He hid it well in public, they said. But not when he was with family or close friends.
Russell Lonser, who oversaw the study, said Seau's brain was "independently evaluated by multiple experts, in a blind fashion."
"We had the opportunity to get multiple experts involved in a way they wouldn't be able to directly identify his tissue even if they knew he was one of the individuals studied," he said.
The NFL, in an e-mail to the AP, said: "We appreciate the Seau family's cooperation with the National Institutes of Health. The finding underscores the recognized need for additional research to accelerate a fuller understanding of CTE.
"The NFL, both directly and in partnership with the NIH, Centers for Disease Control and other leading organizations, is committed to supporting a wide range of independent medical and scientific research that will both address CTE and promote the long-term health and safety of athletes at all levels."
NFL teams have given a $30 million research grant to the NIH.
Before shooting himself, Duerson, a former Chicago Bears defensive back, left a note asking that his brain be studied for signs of trauma. His family filed a wrongful-death suit against the NFL, claiming the league didn't do enough to prevent or treat the concussions that severely damaged his brain.
Easterling played safety for the Falcons in the 1970s. After his career, he suffered from dementia, depression, and insomnia, according to his wife, Mary Ann. He committed suicide last April.
Mary Ann Easterling is among the plaintiffs who have sued the NFL.