Spain lead Argentina 2-1 at the break in Madrid thanks to goals from Diego Costa and Isco, while Nicolas Otamendi has pulled one back.
Costa, restored to the starting line-up for the first time in a year, gave the hosts the lead with a neat finish past Sergio Romero.
The collision between the two was to force the Manchester United goalkeeper off with injury, replaced by Willy Caballero, but despite sustaining a knock the Atletico Madrid striker carried on.
Gonzalo Higuain had previously wasted a glorious chance for the visitors and Argentina – who were without Barcelona star Lionel Messi – were made to pay for their wastefulness when Isco doubled the lead in the 26th minute.
The playmaker found the net after being found by his Real Madrid teammate Marco Asensio in a sweeping Spain move.
Jorge Sampaoli’s side pulled a goal back six minutes from the break as Nicolas Otamendi lost Sergio Ramos at a corner to head home past David De Gea, who will be disappointed not to have done more.
Gerard Pique ended the half with apparent knee discomfort.