Limbrick joins TNS having previously managed Woking, and serving as assistant boss at Grimsby in 2019.
The Australian joined Grimsby in 2018, and worked alongside former Blackpool boss Ian Holloway at Blundell Park. He also had a spell working as academy coach at Southampton.
Christian Seargeant will take the role of assistant boss, having taken charge of the club following Ruscoe's departure.
Mike Harris, chairman and owner of TNS, welcomed Limbrick to the club after what was a 'rigorous and thorough' process of hiring a new boss.
"Anthony’s attention to detail was an influencing factor in his appointment as the club embarks upon on new era, we welcome him to the club, leading the club's target to achieve a place in the group stage of a UEFA Club Competition in the next two seasons." he said.
Limbrick expressed his pride at taking on the role at Park Hall.
"I am delighted and proud to be joining this historic club. The New Saints have great football traditions that is based on winning, and I am going to work hard to make that happen consistently at the football club." he said.
"I am excited to get started and work with the staff and players to have a strong finish to the season. I look forward to meeting you [the fans] all when it is safe to do so, and enjoy this journey together."
Ruscoe was sacked as boss of the Welsh side in March following the club's return to action with a 0-0 draw against third-placed Bala Town.
He was a huge favourite in his Park Hall playing days between 2002 and 2016, won the Welsh top-flight title in two of his three seasons in charge of the Oswestry-based club, as well as three cup wins.
TNS’s grip on the domestic crown slipped when last season was prematurely ended and Connah’s Quay landed top spot on a points-per-game basis.
The club currently sit second in the table, three points behind leaders Connah's Quay Nomads - having played 22 times.