Nilmar added gloss to the score line with a tap-in after substitute Jefferson Montero's dazzling wing-play, and Francisco Chica saw red for petulant challenge five minutes from time to cap a thoroughly unpleasant evening for the visitors.
Both fixtures between these two sides failed to produce a single goal last season, but Espanyol's 3-1 victory over Getafe last week left the Periquitos feeling confident coming into this match.
Striker Pablo Osvaldo - who scored twice against Getafe - looked particularly threatening in the opening stages, forcing a tremendous, fingertips save from Diego Lopez in just the fourth minute.
The keeper was called into action again just minutes later to tip another curling effort around his left post, and was rewarded for his heroics when Giuseppe Rossi made the breakthrough against the run of play in the 24th minute.
The impressive Borja Valero - a summer loan signing from West Bromwich Albion who spent last season at Real Mallorca - played a clever reverse pass from the by-line to Rossi, who confidently stroked the ball past a helpless Carlos Kameni.
Valero was a constant thorn in Espanyol's side, keeping Villarreal's counter-attacking football ticking over with crisp, one-touch passes, and got the goal he deserved with half an hour played.
After some scrappy defending in the visitors' penalty area, the ball broke to the 25-year-old, who took a touch and slammed the ball perfectly inside Kameni's left post.
The scoreline flattered Villarreal, who had been second-best for much of the early stages, but Espanyol repeatedly failed to find an answer to the home side's rapid counter-attacking football.
Espanyol set out their stall early in the second half, committing more men to the attack and leaving huge gaps in the midfield right from the off.
It was a high-risk strategy from manager Mauricio Pochettino, and Villarreal punished them for it with a crucial third goal 10 minutes into the second half.
20-year-old centre-back Mateo Musacchio stormed into the area completely unmarked, and drew a clumsy challenge from the onrushing Kameni.
Referee Eduardo Gonzalez immediately pointed to the spot, and Giuseppe Rossi stepped up to confidently pass the ball into the bottom right corner for 3-0.
Pochettino introduced Ivan de la Pena on the hour mark to try and salvage something for the tiring visitors, but Juan Carlos Garrido's 70th-minute introduction of Jefferson 20-year-old Jefferson Montero proved to be the more influential decision.
The young winger dazzled on the left flank, and put the fourth goal on a plate for Nilmar with an unselfish low ball square in front of goal.
Espanyol failed to deal with Montero's constant movement, and Francisco Chica eventually took it upon himself to stop the young winger with a dangerous hack from behind.
The referee - who had already shown 11 yellow cards in an aggressive, combative match- immediately showed the Espanyol full-back a deserved red card, sealing a horrible day out for the Catalan side.