The resounding victory for the team known as "yellow submarine" lifted them above Sociedad into fifth on 34 points at the halfway stage of the season, two ahead of the San Sebastian-based side and two behind another Basque club, fourth-placed Athletic Bilbao.
It was the latest evidence they fully deserve to be playing among the elite of Spanish football after spending a year in the second division last term.
Mexican Dos Santos fired them ahead in the 17th minute before crossing for Nigerian Uche to make it 2-0 in the 27th.
Dos Santos, a product of Barcelona's academy who has also had stints at Ipswich Town, Galatasaray and Real Mallorca, grabbed his second six minutes later as Sociedad were swept aside by the home side's intensity and attacking verve.
Uche completed his double from another Dos Santos assist 10 minutes into the second half and Moises Gomez added a fifth in the 58th before Imanol Agirretxe pulled one back for Sociedad on the hour.
Villarreal had not won at home since the end of October and the victory will give them a boost for their next game on Thursday, when they host Sociedad again in the last 16 of the King's Cup.
Last week's first leg in San Sebastian ended 0-0 and the winners of the tie will play Almeria or third-tier Racing Santander in the quarter-finals.
"We were really keen to start winning at home again after a long time without a victory," Villarreal fullback Mario Gaspar told Spanish television broadcaster Cuatro.
"I think we enjoyed ourselves on the pitch, you could see that, and now we have to focus on Thursday as we are also very excited about the Cup," he added.
"I hope that the season continues for us in the same vein and we can finish in the best way possible."
Champions Barcelona and Atletico Madrid are level on 50 points at the top after they drew 0-0 at the Calderon on Saturday and third-placed Real Madrid closed to within three points of the leaders when they won 1-0 at Espanyol on Sunday.