The debutant turned in a man-of-the-match performance as Paul Ince's troops eased into the third round of the Carling Cup.
Grimsby's Tom Newey fired the visitors into a surprise early lead, but it was one-way traffic from then on.
After scoring the first Rovers goal, Villanueva set up strike partner Matt Derbyshire for the second. The England starlet then teed up Brett Emerton for the third, before glancing home Morten Gamst Pedersen's cross to seal an emphatic win.
Rovers started brightly, with Derbyshire sending two efforts just over the bar inside the opening three minutes, but it was the visitors that made the early breakthrough.
Villanueva seemed hard done by when a free-kick was awarded just outside the Rovers box and set-piece expert Newey smashed the ball past the unsighted Jason Brown and in off the underside of the bar.
Rovers responded well and were soon back on level terms. Villanueva fired a warning sign when his eighth-minute effort had to palmed around the post but, just ten minutes later, he went one better with a delightful left-foot curler into the bottom corner of Phil Barnes' goal.
Chile's Player of the Year was running the show for Rovers, who completed the turnaround just past the half-hour mark.
Shortly after sending a header straight into the arms of Barnes, Villanueva twisted and turned on the edge of the Grimsby box. His deflected shot was only parried by the Mariners keeper and Derbyshire was on hand to gobble up the rebound.
Villanueva almost grabbed his second with another sweet left-foot strike from long range, before Derbyshire turned provider to make it 3-1.
In the 39th minute, the England Under-21 striker laid the ball off to Emerton who curled the ball into the top right-hand corner of the net.
Less than 60 seconds later, the Australia international's fierce right-foot volley forced a fantastic fingertip save from Barnes.
Fresh from a half-time team-talk, the visitors came out with renewed optimism at the start of the second half and almost pulled a goal back less than 30 seconds in.
Peter Till played in Nick Hegarty, whose first effort was saved by Brown and his second looped over the unguarded net.
But any hope of a comeback was soon extinguished when Derbyshire netted his second on 55 minutes. Pedersen supplied the cross and the Blackburn-born forward flicked the ball home at the near post.
Rovers really ought to have added to their total, with Derbyshire twice heading wide of the target while Pedersen's sliding effort was kept out at point-blank range.
Derbyshire then thought he had extended the home side's lead with a precise header from substitute Paul Gallagher's cross, but he was denied his first-ever hat-trick by the linesman's flag.
The 22-year-old saw two more efforts saved late on but it was fitting that the game should end with new Ewood favourite Villanueva rattling a free-kick against the top of the bar.