The problem is not a recurrence of the cruciate ligament damage Blackstock sustained against Cardiff in 2010 which kept him out for 12 months.
The 27-year-old suffered the injury in training ahead of Leeds' Championship game against Blackburn nine days ago.
"Unfortunately Dexter has got to go back to Nottingham Forest," Leeds assistant manager Nigel Gibbs confirmed.
"He has got to have an operation on his knee, which is obviously disappointing for him but also for us.
"He fitted in really well and you can see from his performances how much he brought to the team. We are sad to see him go back.
"He came on as a substitute in the first couple of games but then he played his part in the team. He really knitted the team really well and had a good relationship with Ross (McCormack) up there.
"We never really saw the best of him but he contributed while he was here and I think he could have done really well for us."
Blackstock joined Leeds in October and made four appearances during his time at Elland Road.
The striker made an immediate impact, scoring on his debut at Huddersfield, and he also created two of McCormack's four goals at Charlton.
He was set to remain at Leeds until January 25 2014.