By doing so, they ensured that they will be at home in the second leg of the Championship play-offs, with a top-four finish now certain.
Robert Earnshaw's 15th goal of the season put them in control before an own goal from Bondz N'Gala ensured Forest doubled their advantage before the break.
A strike from substitute Paul Anderson in the 92nd minute completed Plymouth's misery.
Given their remarkable home form, it was not a shock to see Forest take control early on.
But, while they found chances simple to create, the home side found them harder to convert, as Nathan Tyson fired over when clean through and Earnshaw saw a rising effort deflected wide after scampering clear himself.
Forest were playing some flowing football and it was no surprise when the breakthrough came in the 18th minute, as a superb pass from Radoslaw Majewski split the visitors' defence again.
The Pole looked one way and played the ball another, finding the feet of Earnshaw, who lifted a simple, precise chipped finish over the advancing David Stockdale and inside his right-hand upright.
Forest got a second goal in bizarre circumstances as a Guy Moussi cross from the right caused havoc in the Plymouth rearguard, with keeper Stockdale seeming to punch the ball into defender Bondz N'Gala, with the rebound then flicking an oblivious Blackstock, before the ball bobbled over the line.
The goal came after Plymouth had just tested Forest keeper Lee Camp - named player of the season prior to kick-off - for the first time.
Alan Judge connected crisply with a driven shot from the edge of the box, but the Reds skipper got down well to parry on his line.
After the break it took a remarkable sliding block from Wes Morgan to deny Bradley Wright-Phillips, just as it seemed the Plymouth man was certain to provide his side with a life-line.
Although Tyson saw a shot pushed into the side netting after he had turned superbly on the right side of the box and Moussi sent a looping header narrowly over.
It was not until injury time that Forest emphasised their advantage as McGugan's incisive pass gave Anderson the chance to slot home from close range.