The duo, who already own the NBA's Philadelphia 76ers and the NHL's New Jersey Devils, will join chairman Steve Parish in control at Selhurst Park.
A statement from the Premier League club read: "Crystal Palace Football Club is delighted to announce that it has today signed a deal with investors Josh Harris and David Blitzer. The deal will see chairman Steve Parish, Josh Harris and David Blitzer take control of the club in a general partnership structure.
"They will be joined by a number of other investors in a limited partnership that will include current CPFC2010 shareholders, Stephen Browett, Jeremy Hosking and Martin Long, who will all retain a substantial shareholding.
"All shareholders have agreed an initial £50million injection of capital for the development of the stadium, with more to follow. This will give fans the first-class facilities they deserve.
"The deal offers the club the best opportunity to build on the enormous progress made over the last five years, during which time it has come out of administration and established itself as a thriving, financially secure member of the Premier League.
"It ensures that, while overseas investors are joining us, the heart and soul of the club remains in south London."
The deal has been long in the offing, with Palace manager Alan Pardew saying this week that investment was on the agenda when he agreed to take charge of Palace in January.
Harris, Blitzer and Parish will each own an 18 per cent stake in Palace under the new arrangement.
A statement from chairman Parish read: "I'm delighted that Josh and David have agreed to make this investment and join me in shaping the future of Crystal Palace.
"I have had the great pleasure of getting to know them both over the past 18 months and I am sure they will be a huge help to me and add an enormous amount of value.
"I am looking forward to getting started with them and continuing to drive this great football club to ever great heights. I would like to thank Stephen, Jeremy and Martin, as well as all the club's supporters, for their incredible support over the past five years and I am thrilled they will retain a shareholding for the next part of the journey."
A joint statement from Harris and Blitzer read: "We couldn't be more excited to be joining the Crystal Palace family. We were drawn to the club's rich history, exciting brand of football, strong leadership and, above all, its passionate fans.
"We've had the great pleasure of getting to know Steve and have the utmost respect for him and his partners, Stephen, Jeremy and Martin.
"We look forward to supporting Steve in his role as the operating co-owner and leader of the club. Crystal Palace has a storied legacy, a bright future and we're proud to become a part of it."
Palace sit sixth in the Premier League table, having been rejuvenated under Pardew's leadership this year, avoiding relegation last season and mounting an early push this term for a place in the UEFA Europa League.
