The game quickly became a foregone conclusion when Levante goalkeeper Keylor Navas tripped Uche in the box with just nine minutes gone and was sent off.
Bruno Soriano converted the spot-kick, and then Uche sealed the win with two second-half goals.
The win not only cemented the Yellow Submarine's grip on the final Champions League spot, but also marked the club's strongest ever start to a campaign in La Liga.
Levante forward Nabil El Zhar had the first shot of the game with less than a minute gone, but, that aside, Joaquin Caparros' side struggled from the start against an energetic Villarreal.
The visitors' early pressure soon had the desired impact, leading to the incident which would have an irreversible effect on the game.
With nine minutes played, Uche raced into the box and took the ball beyond Navas, who kicked out at the Colombian as he was going past.
The referee had no hesitation in sending off the Costa Rican goalkeeper. Substitute Javier Jimenez came on, with midfielder Jordi Xumetra making way.
It was Jimenez's first appearance for Levante and it began with Bruno sending him the wrong way from the spot with a finish which oozed confidence.
Levante are not a team known for their ability to produce free-flowing attacking football at the best of times, so, a man down and a goal down with the best part of 80 minutes left on the clock, their hopes of defeating Marcelino's high flyers were already slim.
They were dealt a further blow when their focal point in attack, Baba Diawara, was taken off injured midway through the first half. Their best chance of the game was a header from Pape Diop, which was saved by Sergio Asenjo.
Five minutes before the break Hernan Perez almost scored what would have been a contender for goal of the weekend, striking a volley on the turn from outside the area which clipped the upright.
And just before the half-time whistle sounded, Bruno also came close to a second goal, shooting from just inside the area but Jimenez pushed it away for a corner.
The goalkeeper was also at hand in the second half to deny Manu Trigueros in a one-on-one, as a second Villarreal goal looked more and more inevitable.
Jonathan Pereira and Cani both squandered chances to score, while Javier Aquino shaved the far post, opting to go for goal with Uche waiting in the middle.
The Colombian striker was furious with his Mexican team-mate for not squaring to him, but with 16 minutes remaining he got the goal he desired and killed the game off.
The striker positioned himself between two Levante defenders and controlled a through ball from Bruno before slotting past Jimenez.
In the dying moments Uche scored again, producing a spectacular overhead-kick to send a loose ball into the net, after substitute Jeremy Perbet had struck the bar.