King has signed a two-year deal and replaces Brian Horton, who left Moss Rose after the Silkmen dropped into the Blue Square Bet Premier having finished bottom of League Two.
He told Macclesfield's official website: "Macclesfield Town represents an exciting challenge for me. I want to manage at the highest level possible and to be given the chance to lead the Silkmen to an early return to the Football League is a great opportunity."
King led Lewes to five promotions in seven seasons during two spells at The Dripping Pan. He departed for a second time by mutual consent in January after being suspended a week earlier for reasons the club refused to reveal.
Macclesfield owner Amar Alkadhi said: "With more than 50 serious applications we had plenty of options, but this time I wanted to do something new and exciting.
"Steve King is a young, hungry manager with real ambition and a reputation for playing fast, flowing football. I'm backing him to bring the feel-good factor back to Moss Rose after three difficult seasons."