The duo had not played together since their disastrous showing in the 5-1 defeat to the Netherlands at the World Cup before the Euro 2016 qualifier in Huelva.
Pique and Ramos helped provide the bedrock of Spain's consecutive European Championship titles and the World Cup which they sandwiched, and returned to that form as Spain clinched their third Group C triumph from four games.
Spectacular goals from Isco, Sergio Busquets and Pedro highlighted the triumph, but Del Bosque was quick to look elsewhere for inspiration, including his rejuvenated central defenders.
"When we find the strength of Pique and Ramos, we have a head start," he said.
"The midfielders were very serious and if we find the strength of that core we have a lot to look forward to.
"Juanfran and Santi Cazorla linked up a lot and Juanfran got forward a lot. I think he can feel happy."
At the other end of the pitch - and the international scale - Alvaro Morata made his senior Spain debut in the clash, replacing Isco for the game's final 10 minutes.
"I am the happiest man in the world after this debut," the Juventus striker told Sky Sport Italia.
"It was a great Isco goal and I am happy for him. The crowd made everything just fantastic. We could've scored more goals, but the three points were important.
"Now I want to stay in the national team and that's why I'm here."
