The 55-year-old former Yeovil Town, Brighton, Leyton Orient and Cardiff boss has agreed a three-year deal at The Valley.
Slade left his role as head of football with the Bluebirds last week.
He replaces Jose Riga, who resigned as head coach on May 7 after the end of the Championship campaign, which the Addicks finished in 22nd place.
His first permanent managerial post was at Boro, and when he arrived in November 2001 the club were adrift at the bottom of the Conference and looking doomed.
Slade’s first match in charge resulted in a home win over Farnborough Town but the next three games yielded just one point.
However a remarkable run of 39 points from the final 19 games of the season meant the Seasiders finished 12th.
He was hailed as a hero by the Boro fans and his stock rose when taking the team to fourth position by Christmas in the 2002–03 season.
In January 2003, two days after the club went into administration, Slade tendered his resignation.
The fans presented a tearful Slade with a petition at the next game and on the Monday morning he changed his mind.
The following season saw mixed league performances, but a superb FA Cup run which saw victories over Hinckley United, Doncaster Rovers, Port Vale, and finally Southend United following a replay, meant a glamorous home tie with Premier League Chelsea. Despite losing 1–0 the Seasiders put up a tremendous battle.