The filing comes days after a jury ruled that he must pay $5m to a woman suing over a sex tape case.
50 Cent's 2003 album Get Rich or Die Tryin' catapulted him to global fame.
Real name Curtis James Jackson III, the Grammy-award winning rapper's business interests have included clothes, boxing, drinks, and mining.
His stake in VitaminWater reportedly netted him tens of millions of dollars when Coca-Cola bought the drinks brand in 2007.
Chapter 11 allows companies time to re-organise their finances while protecting them from creditors' demands.
The court case stemmed from a video in which the rapper is accused of adding a commentary to a tape that the woman made with her boyfriend. The tape was then leaked online.
In addition to the $5m penalty, the jury was due this week to consider punitive damages in the invasion-of-privacy lawsuit. However, it was unclear if this would go ahead.
Manhattan Supreme Court Justice Paul Wooten had requested that 50 Cent disclose details of his finances.
'Business as usual'However, the rapper's lawyers told the court that he had filed for Chapter 11 in Connecticut, where he owns a mansion he bought from boxer Mike Tyson.
Later, a lawyer for 50 Cent (Mr. Jackson), William A Brewer III, said his client's business operations would continue.
"Mr Jackson's business interests will continue unaffected in the ordinary course during the pendency of the Chapter 11 case,'' the attorney said in a statement.
It added: "This filing for personal bankruptcy protection permits Mr. Jackson to continue his involvement with various business interests and continue his work as an entertainer."
50 Cent, aged 40, has sold more than 30 million albums and won a Grammy Award in 2010. The star's latest film role is in the upcoming "Southpaw," in which he plays a boxing promoter.
In May, Forbes estimated 50 Cent's net worth at $155m.