The new Manchester City forward is competing for attention with long-standing regulars Fernando Torres and David Villa, who were left out of the squad for the Ecuador trip, as well as Roberto Soldado and Fernando Llorente.
Known in Spain as the "Beast of Vallecas" after the Madrid neighbourhood where he was born, Negredo is noted for his power and physique, but scored a wonderful improvised goal with a subtle touch to open the scoring in their 2-0 friendly win.
Santi Cazorla's low cross to the near post saw Negredo left with little room to move, so he let the ball pass between his legs and flicked it over the keeper with his trailing left foot.
"I saw the keeper was diving and it was the only way I could find to shoot," the 27-year-old, who played the first half as Spain's solitary striker, told reporters.
"I have tried to make the most of the opportunity. The boss has given me minutes and I am pleased."
Del Bosque has demonstrated a willingness to forgo playing with a traditional centre forward, preferring players such as Cesc Fabregas as a 'false nine' arriving from midfield, so it was rare to hear praise of Negredo's performance.
"We expect a lot from Negredo and I like the way he moves in the area. Today he has been very good," Del Bosque said.
"Negredo finished with a small problem, nothing serious, and I hope he will be able to play for his club this weekend."
New Juventus forward Llorente played the second half and headed just wide late on, while Del Bosque also handed three young players their debuts in Cristian Tello, Inigo Martinez and Koke.
Spain were also without first-choice midfielders Xavi, Xabi Alonso and Sergio Busquets, but Arsenal's Cazorla impressed as he took the helm in the middle, setting up the first and scoring the second from Tello's backheel.
Cazorla has been on the fringes of the squad since helping the national team to victory at Euro 2008, but could be set for a prominent role over the coming year as he deputised well for the absent Xavi.
"There are young people coming through which is good," Del Bosque added.
"And there are other footballers who do not play so often, as is the case with Cazorla and (Raul) Albiol, but who always rise to the occasion. We have great confidence in this group because they have the hunger to keep on winning."