Redfearn has previous experience managing in the women's game with Doncaster Rovers Belles where he won the league in 2018 and Liverpool Women.
That WSL 2 title with Belles in 2018 was their first trophy since 1994.
He replaces Carla Ward at the helm who departed the Blades earlier this summer and is now the head coach at Women's Super League club Birmingham City.
The 55-year-old has also managed Leeds United and Rotherham United in the men's game before most recently working at Newcastle United with their Under 23 side.
Redfearn will take charge with immediate effect ahead of next Sunday's opening day FA Women's Championship fixture away to London City Lionesses.
Speaking to the club website, he said: "It's very exciting. It's a massive club and the women's team has made good strides over the past couple of seasons, so it's a good place to be.
"I really enjoyed my time at Belles and Liverpool, women's football is really on the up and Sheffield United have been a big part of that it's a really exciting place to be."
Redfearn will be a familiar face for some of his new players including Leandra Little, Jade Pennock, Sophie Walton and Emily Batty who he coached at Belles.
Redfearn added: “It's important because they know how I work and it helps the transition for the rest of the girls.
"It's a case of trying to get us in a position where we can have a really positive season again.
"Those that were at the Belles, they know the route, they know the way, they know how to get out of this division."
Chief executive officer Stephen Bettis said: "We are delighted to welcome Neil, he is experienced in women's football and we hope he will help Sheffield United continue on the upward trajectory of the past couple of seasons."
As a player, Redfearn made over 850 appearances at clubs including Barnsley, Crystal Palace and Doncaster.