Bruce only arrived at the Leasing.com Stadium at the end of October, succeeding Mark Duffy.
He went on to win nine of his 15 league games in charge of Macclesfield, drawing three and losing three. Such form means they currently occupy the final play-off spot and are just two points behind second-placed Hyde United.
During his time in charge, Bruce also led the club to the quarter-finals of the FA Trophy, where they will host Southern Central League side Coalville Town.
His final game in the Macclesfield dugout was a 5-3 home win against Ilkeston Town on Saturday.
It has not yet been confirmed which EFL side Bruce - who has previous Football League coaching experience as part of the backroom staff at West Brom - will be joining.
In a statement, Macclesfield said: "Whilst being disappointed that Alex has decided to leave the club at this stage of the season, we wish him well in his future career.
"A further statement will be communicated regarding our new Coaching Team in due course."
The Silkmen return to action on Saturday with a trip to Atherton Collieries, who are currently in the Northern Premier League's relegation zone, five points from safety.
Photo credit: Macclesfield
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