Hughes, who finished his playing career at Boro before taking over as joint-manager with Paul Foot, has signed a three-and-a-half year deal at the National League club.
As a manager at Boro, Hughes, alongside Foot, made a hugely positive start to life in the Evo-Stik North, but results turned against the pair and they left to be replaced by current boss Steve Kittrick at the end of 2015.
Wrexham AFC board of directors commented: "Bryan is an excellent coach who has a strong affinity for the Club. His appointment signals our intent to go back to the model which has seen us progress on the pitch and again become competitive in the League.
"Bryan will be completely focussed on building momentum in the final 15 games of the season as we look to achieve a successful end of the season."