Di Santo has been a long-term target for Blackburn boss Sam Allardyce, who has spent much of the summer trying to conclude a deal.
Allardyce was initially uncertain whether new Chelsea manager Carlo Ancelotti would be willing to let the Argentine youngster leave Stamford Bridge.
However, after featuring for the Blues on their pre-season trip to America, Di Santo has been given permission to move to Ewood Park.
The 20-year-old will stay with Rovers initially until January, but the deal could be extended until the end of the season if he is not required back by Chelsea.
Di Santo joined Chelsea from Chilean side Audax Italiano in January 2008 and made his first-team debut as a substitute against Tottenham in August last year.
He has yet to start a senior game for the Blues and has also failed to score in his 16 appearances from the bench.
The signing will help to fill the void at Blackburn created by Roque Santa Cruz's departure to Manchester City, with Allardyce also closing in on a deal for Croatian hot shot Nikola Kalinic.