The 27-year-old moved to Ewood Park for a reported £3million fee in July 2012, but suffered an anterior cruciate ligament injury soon after joining the Lancashire club.
Best failed to establish himself as a starter at Blackburn when he returned to fitness and he was shipped out on loan to fellow Championship side Sheffield Wednesday in February, where he scored four goals in 15 league outings.
The former Newcastle United man had been linked with a return to Hillsborough, but Derby - who lost to QPR in May's Championship play-off final - soon emerged as favourites for his signature.
"I'm extremely pleased that we have been able to sign Leon Best on loan for the season," Derby manager Steve McClaren told the club's official website.
"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.
"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."
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