Best only started five games for Blackburn last season after missing a large chunk of action the previous year due to a cruciate knee ligament injury, though he played 15 games on loan at Sheffield Wednesday.
Under the terms of his loan, the 27-year-old will be unavailable to play against his parent club when the two sides meet at Ewood Park next month as well as the return league fixture in January.
Derby manager Steve McClaren said: "I’m extremely pleased that we have been able to sign Leon Best on loan for the season.
"He is a player with Premier League and Championship experience, knows how to score goals and he will provide a different option in our attacking armoury."
He added: “We have been keen to add to our frontline during the summer and Leon is someone that we have discussed at length.
“I’ve spoken to the player and believe he views this loan move as a fresh start, and I can sense he is determined to make the most of the opportunity.”
The Nottingham-born striker moved from Notts County to Southampton as a schoolboy in 2004 and made his Premier League debut for the south coast club later that year.
Best left to join Coventry in 2007 and after more than 100 appearances for the Midlands side he moved to Newcastle for a fee of £1.5m.
After two-and-a-half years on Tyneside, Best moved to Blackburn but has seen his Rovers career disrupted by injury.