Moments later, La Roja threatened again when Gerard Pique found himself a few yards from goal, but failed to direct his close-range header past the Juventus stopper.
Spain made their domination count 10 minutes after the break when Sergio Busquets's slide-rule pass played Vitolo through on goal and, as Buffon missed the ball, the Sevilla winger slotted into an empty net.
Just after the hour mark, the introduction of Ciro Immobile seemed to stir a response from the hosts and the former Borussia Dortmund forward was inches away from connecting with Alessandro Florenzi's cross.
With a quarter of the game left, Vitolo nearly doubled his personal tally for the evening as he again latched on to a through-ball, but this time placed his shot wide with only Buffon to beat.
Indeed, the home side thought that they were ahead after Andrea Belotti slotted home from close range, but his strike partner Immobile was adjudged to have impeded De Gea and both sides settled for a point.