Seau died at age 43 of a self-inflicted gunshot in May. He was diagnosed with CTE, based on posthumous tests, earlier this month.
An Associated Press review in November found that more than 3,800 players have sued the NFL over head injuries in at least 175 cases as the concussion issue has gained attention in recent years. The total number of plaintiffs is 6,000 when spouses, relatives and other representatives are included.
Scores of the concussion lawsuits have been brought together before U.S. District Judge Anita B. Brody in Philadelphia.
"Our attorneys will review it and respond to the claims appropriately through the court," the NFL said in a statement Wednesday.
Helmet manufacturer Riddell Inc., also is a defendant, with the Seau family saying Riddell was "negligent in their design, testing, assembly, manufacture, marketing, and engineering of the helmets" used by NFL players. The suit says the helmets were unreasonably dangerous and unsafe.
Riddell issued a statement saying it is "confident in the integrity of our products and our ability to successfully defend our products against challenges."
Seau was one of the best linebackers during his 20 seasons in the NFL, retiring in 2009.
Plaintiffs are listed as Gina Seau, Junior's ex-wife; Junior's children Tyler, Sydney, Jake and Hunter, and Bette Hoffman, trustee of Seau's estate.
The lawsuit accuses the league of glorifying the violence in pro football, and creating the impression that delivering big hits "is a badge of courage which does not seriously threaten one's health."
It singles out NFL Films and some of its videos for promoting the brutality of the game.
"In 1993's 'NFL Rocks,' Junior Seau offered his opinion on the measure of a punishing hit: 'If I can feel some dizziness, I know that guy is feeling double [that]," the suit says.
The NFL consistently has denied allegations similar to those in the lawsuit.
The lawsuit claims money was behind the NFL's actions.
"The NFL knew or suspected that any rule changes that sought to recognize that link [to brain disease] and the health risk to NFL players would impose an economic cost that would significantly and adversely change the profit margins enjoyed by the NFL and its teams," the Seaus said in the suit.
In the final years of his life, Seau went through wild behavior swings, according to Gina and to 23-year-old son, Tyler. There also were signs of irrationality, forgetfulness, insomnia and depression.
The NFL fined New England quarterback Tom Brady $10,000 for an "aggressive slide" in Sunday's AFC Championship Game against Baltimore, when he raised his right leg and kicked Ed Reed in the thigh. Brady reportedly apologized to Reed in a text message.
* Oakland hired Tony Sparano as an assistant head coach who will work with the offensive line. Sparano spent last year as the Jets' offensive coordinator.