Victor Genes' men led courtesy of Roque Santa Cruz's deflected strike late in the first half, before the hosting Peruvians had striker Paolo Guerrero sent off in the 67th minute.
But a stunning cameo from substitute Ascues saw the Peruvians steal victory in front of their home fans.
Ascues equalised when put through by Cristian Benavente moments after gracing the field in the 72nd minute, before the Universidad San Martin man struck the winner eight minutes later.
There was late drama, just as there was in the clash in Luque, with each of Peru's Yordy Reyna and Paraguay's Derlis Gonzalez - both substitutes - sent off in injury time.
Substitute Ascues, though, had an immediate impact on the contest, netting twice in eight minutes to provide the answer to coach Pablo Bengoechea's attacking woes.
The Paraguayans had created the better chances in the first half, Paulo da Silva's volley in the fourth minute clearing the crossbar before Santa Cruz placed his header wide moments later.
Instead, Guerrero's battle with Gustavo Gomez was the centre of attention - with the Peruvian front man gradually growing frustrated throughout the opening half and fortunate to stay on the park.
His night would have been ended even earlier had powerhouse club Corinthians had their way, as Guerrero's inclusion ruled him out of a key domestic clash in Brazil.
Guerrero claimed he was elbowed in the face by Gomez earlier in the contest before his lash out after the half-hour mark, and was later tackled to the ground by Cristian Riveros - as the attention on the number nine intensified.
Guerrero's night eventually did end early, as he earned his second yellow of the match in the 67th minute for a deliberate handball foul.
And the 22-year-old completed the stunning comeback by getting on the end of a sweeping Peru move that saw them move the ball from the left sideline in midfield to the attacker on the right, and he finished at Villar's near post.
