The team announced the move in a release Wednesday night.
BREAKING: Kathryn Smith is the Bills new special teams quality control coach, the first full-time female NFL coach! pic.twitter.com/r2MkWX4pR3— Buffalo Bills (@buffalobills) January 21, 2016
Smith was an administrative assistant this season for Bills assistant coaches under Rex Ryan, with whom she has worked for seven years.
She spent the previous 12 seasons working for the New York Jets in various capacities, including a player personnel assistant from 2007-13. Ryan became Jets coach in 2009. Smith served as Ryan's assistant in 2014, his final season in New York before he was fired and then hired by the Bills.
In her new role, Smith will assist special teams coordinator Danny Crossman and his assistant Eric Smith.
"She certainly deserves this promotion based on her knowledge and strong commitment, just to name a couple of her outstanding qualities," Ryan said in a statement released by the team. "She has proven that she's ready for the next step, so I'm excited and proud for her with this opportunity."
Smith becomes the latest female assistant to break the gender barrier in North America's major professional sports.
She follows in the footsteps of Jen Welter, who last summer served a six-week training camp internship coaching inside linebackers for the Arizona Cardinals.
In August 2014, former WNBA player Becky Hammon was hired to San Antonio Spurs coach Gregg Popovich's staff in becoming the NBA's first full-time paid female assistant coach.
Last month, the Seattle Mariners hired Amanda Hopkins as an area scout. In announcing the hiring, the team said Hopkins is believed to be the first female hired as a full-time scout by a major league team since the 1950s.
In promoting Smyth, Ryan said he consulted with Cardinals coach Bruce Arians.
"You can see the success some of these young ladies are having in the coaching profession, such as the young lady that is an assistant to coach Popovich at the San Antonio Spurs, and realize how exciting this is for women like Kathryn Smith as well as the Bills organization," Ryan said.