The Belgium international has sealed a return to his homeland after spending three years with the Portuguese giant.
The 26-year-old had been linked with a move to PSV, but has opted to return to the Pro League, three years after moving to Portugal from Standard Liege.
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After 111 appearances for Porto in all competitions, Defour was deemed surplus to requirements and becomes the fifth player to depart ahead of the new season.
In an announcement to the Portuguese Securities Market Commission (CNVM), Porto confirmed the deal with Anderlecht, with the fee potentially rising to €6.5 million.
Defour represented Belgium during the recent World Cup in Brazil, but saw his tournament end early after a red card against South Korea.
Anderlecht has yet to confirm the deal and present Defour as a new signing.