Alcacer, the Bundesliga's top scorer with an average of a goal every 14 minutes, continued his fine form as he turned out for his country for the first time since 2015.
Truth be told the visitors were a class above throughout, with Wales having barely got a touch on the ball by the time Spain took the lead with eight minutes gone.
Suso's cross from deep on the right wasn't convincingly cleared and after a small amount of penalty-box pinball, the ball dropped for Alcacer to rifle into the top corner from just inside the box to justify his inclusion from the off.
For all of Spain's fluid football and dominance of possession, their second of the game game from some frankly shameful defending from the home side, who managed to leave Sergio Ramos of all people completely unmarked from a free-kick.
Suso clipped the ball in and Ramos peeled away to the back post to plant a header back across Wayne Hennessey and into the far corner to double the lead.
It was starting to look like it could be disastrous evening for the Welsh andbefore the half-hour mark they were even further behind, as Alcacer reacted quickest to volley home first time from 12 yards after a mix-up between Harry wilson and Joe Allen.
Spain took their foot off the gas slightly at that point and they came close to being caught cold as Ethan Ampadu looped a header against the outside of the post nine minutes before the break, though David De Gea looked to have it covered.
The half-time whistle brought a raft of changes, with five in total across the two sides, but Spain's dominance continued.
The home side were soon forced into another change in personnel as young Ethan Ampadu departed with a knock, making him a doubt to face Ireland in the UEFA Nations League on Tuesday.
That change was sandwiched by chances for Alvaro Morata and Alcacer, but Hennessey did well to deny the former, whilst the latter could only head a Gaya cross over the bar.
Suso, who was tidy throughout, came inches away from scoring the goal of the game just before the hour mark as he cut in off the right and looked for the far corner, only for his dipping strike to clip the bar on its way over.
Substitutions continued to break up the flow of the game, with debutant Jonny doing well to deny Sam Vokes at one end, before Marc Bartra added some further gloss to the scoreline at the other.
The Real Betis defender planted a beautiful header into the far corner from a Suso corner to make it four, with only the offside flag preventing Iago Aspas from adding to the lead further with 12 minutes to go.
There was still time for some late Wales pressure, though, with Ryan Giggs' men getting a late consolation as Vokes headed home the impressive David Brooks' delightful ball in from the right in the 89th minute.
Spain continue their 100% record under Luis Enrique ahead of their meeting with England in Sevilla on Monday, whilst Wales certainly have work to do as they prepare for the trip to Ireland the following day.
October 11, 2018