Brady, 73, died of pneumonia, the family said.
"Sarah courageously stepped up after Jim was shot to prevent others from enduring what our family has gone through, and her work has saved countless lives," their statement said.
James Brady, President Ronald Reagan's press secretary, was shot in the head by John Hinckley Jr. during his attempt to assassinate Reagan in 1981. Brady spent the rest of his life in a wheelchair, advocating against gun violence.
He died in August.
Sarah Brady was also involved in gun violence prevention for the past 30 years. She was the chairwoman of the Brady Campaign to Prevent Gun Violence and the Brady Center to Prevent Gun Violence from 2000 until she died.
The National Rifle Association said its thoughts and prayers were with the Brady family.
"Although we disagreed on public policy, Sarah Brady was an honorable American who we always respected," the gun rights organization said.
On the Brady Campaign's website
, she said she got involved in gun control after her young son picked up what she thought was a toy gun on the seat of a friend's pickup. Her son started to wave it around and she took it from him. It was not a toy, she said, and she fumed over what she imagined could have happened. The loaded gun was much like the one used to shoot her husband.
"It just hit me like a ton of bricks," she told CNN in 2013. "So I asked Jim if he felt comfortable with me speaking out, and he said, 'Of course.'"
After that, the Bradys made it their business to be gun control activists.
Despite budgets that were just a fraction of the gun lobby's, the Bradys and their colleagues helped pass federal and state laws, including Maryland's 1988 ban on cheap handguns known as Saturday night specials, 1993's Brady law requiring background checks on certain kinds of gun purchases and a ban on manufacturing and future sales of some military-style firearms, which lasted from 1994 to 2004.
Former President Bill Clinton, who signed the Brady bill in 1993, and former Secretary of State Hillary Clinton said in a joint statement Saturday that the Bradys "were fierce champions of sensible gun legislation."
Sarah Brady "transformed tragedy into a courageous campaign, and because of her work and her remarkable life, American families are safer today," the Clintons said.
Brady Campaign and Center President Dan Gross said in a written statement that few people are responsible for saving as many lives as Sarah and James Brady.
"Our nation has lost a great hero, and I have lost a dear friend," he said. "I am certain that she would want nothing more than to know we are carrying on her and Jim's legacy with the same fiery compassion and dedication that made her so remarkable."
Sen Charles Schumer, a New York Democrat who helped write the Brady bill, concurred.
"She was strong and forceful, sweet and kind, and someone I considered a friend and patriot for decades," he said. "She was a true hero and will be missed by America."
James Brady was one of four people wounded in Reagan's shooting outside a Washington hotel.
Suffering a head wound, it was erroneously reported at one point that Brady had died. He was, however, left partially paralyzed.
Reagan, severely wounded as well, also survived the attack and served two terms as President. Hinckley was found not guilty by reason of insanity in the shooting and has spent the ensuing years in a psychiatric hospital.
The Brady bill was fiercely fought over for seven years before Congress approved it and President Bill Clinton signed it into law in 1993.