The 50-year-old was sacked from his position in charge of Scunthorpe United last week after less than a year at the helm.
"We welcome Russ Wilcox to York City Football Club," chairman Jason McGill told the club's official website. "We believe he is the right person to take this club forward. He has excellent managerial experience and a track record of success in League Two. He is a hard working individual and an excellent motivator and someone who shares our vision for the club now and in the future."
Wilcox added: "I am delighted to be the new manager of York City Football Club and I'm looking forward to the challenge ahead of me. The club has great potential, with a new stadium on the horizon, and I feel I have the experience to help York City achieve success in League Two.
"I'm looking forward to meeting all the coaching staff and players on Thursday ahead of our home game against Shrewsbury on Saturday. I'm very excited and pleased to be embarking on this new journey."