The Pilgrims had gone nine league games without losing at the Theatre of Greens but could not prevent Daniel Farke's red-hot side from extending their superb run of results.
Argyle emerged with credit from the game, though, especially for their performance in the second half when they made life uncomfortable for Leeds before the visitors grabbed a second goal.
It was always an uphill task for the Pilgrims after they fell behind to a 10th minute goal from Willy Gnonto but despite Leeds dominating the possession it remained 1-0 until the break.
Argyle were able to get on the attack much more often in the second period and had genuine hopes of maybe getting an equaliser until Georginio Rutter doubled Leeds's lead in the 72nd minute and there was no way back for them from that.
For the first time since the Pilgrims lost 3-1 to Swansea City more than four months earlier, they slipped to defeat in front of yet another sold-out Home Park crowd.
Jordan Houghton captained Argyle as he returned to the team as one of four changes from the 2-2 draw at home to Coventry City on Wednesday.
There were also starts for Julio Pleguezuelo, Mickel Miller and New Zealand international striker Ben Waine, who had scored when the Pilgrims lost 2-1 to Leeds at Elland Road in the league earlier in the season.
On-loan Leeds midfielder Darko Gyabi had to miss out for Argyle against his parent club while the trio of Brendan Galloway, Ryan Hardie and Lino Sousa dropped down to the substitutes' bench.
Mustapha Bundu was also named among the substitutes after being ruled out of the previous four games due to a calf injury. Leeds, meanwhile, were unchanged from their 4-0 win away to Swansea City on Tuesday.
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