Chastain, who is now retired from the sport, said she hoped it would help "change things for the positive".
She joins a number of sporting figures helping to research long-term effects of concussion on competitors in sports.
CTE, a degenerative disease, has been found in athletes with a history of repetitive brain trauma.
Chastain, 47, announced on Thursday she would be donating her brain to Boston University, which is leading studies into the effects of multiple concussions and chronic traumatic encephalopathy (CTE).
"It's scary to think about all the heading and potential concussions that were never diagnosed in my life, but it's better to know," she said, speculating about her own experience of head injury during her football career.
CTE is associated with symptoms such as memory loss, depression and progressive dementia.
No female athletes have been found to have suffered from CTE, the New York Times reports, though this may be because the sample size is too small. The disease has been found in a number of male sports stars - including many former American football players.
CTE cases can only be diagnosed after examination of the brain post-mortem.
Chastain's decision follows that of her team mate, Cindy Parlow Cone, who has also decided to donate her brain.
Both women have been calling on football regulators to introduce regulation preventing children under the age of 14 from heading the ball.
Research into CTE has thrown the spotlight on several sports, including American football, horse-racing and rugby in recent months.
A Hollywood film about the effects of concussion on National Football League stars was released last year, starring Will Smith.
In February, it was revealed Ken Stabler, one of the most celebrated quarterbacks of all time, had been suffering from the disease.
Chastain became well known for scoring America's winning goal in a penalty shoot-out against China in the final of the 1999 Women's World Cup.
Images of the football star kneeling on the pitch in her black sports bra, fists clenched, swept around the world, becoming an iconic image for women's football.
US football star Brandi Chastain, who shot to fame in the 1999 Women's World Cup, has pledged to donate her brain to the Concussion Legacy Foundation.