The 19-year-old earned the trust of head coach Erik ten Hag in the 2023-24 campaign, where he played 10 times for the first team thanks to the Red Devils' frequent injury problems at the back.
Kambwala, who joined the Man United academy from Sochaux in 2020, made eight Premier League appearances for the 20-time English champions - three from the first whistle - while also featuring twice in the Red Devils' triumphant FA Cup campaign.
The versatility of the Frenchman came in handy last term too, as he played both centrally and on the right-hand side of defence for Man United, but his contract was due to expire in the summer of 2025.
Despite already seeing their defensive ranks thinned by the exit of Raphael Varane on a free transfer, Man United accepted a reported bid of £8.4m from Villarreal for Kambwala, whom the Red Devils paid a moving tribute to on Monday.
Man United hail Kambwala's "passion and enthusiasm in the heat of battle
"Willy Kambwala fought for his dream, and he lived it. The defender joins Villarreal with nothing but our best wishes for the future," Man United said on X, while also releasing an official statement.
"The popular defender, beloved for his passion and enthusiasm in the heat of battle, departs Old Trafford after making 10 first-team appearances. Willy leaves with the sincere thanks of everyone at Manchester United, and our very best wishes for the next chapter of his career."
Villarreal have confirmed that Kambwala passed his medical tests on Monday, and the 2004-born youngster has signed a five-year contract with the La Liga giants until the end of the 2028-29 campaign.
"The French-Congolese player stands out for his physical strength, his superb ability to win duels and his excellent aerial play," the Yellow Submarine said in a statement. "With his arrival at the Submarine, Marcelino's side are bolstering their backline with muscle, talent and a lot of projection."
Kambwala becomes the eighth player to leave the Theatre of Dreams this summer, following Varane, Anthony Martial, Donny van de Beek, Shola Shoretire, Alvaro Fernandez, Brandon Williams and Omari Forson out of the door.
Man United to replace Kambwala with Ten Hag favourite?
With Kambwala's exit now official, Ten Hag currently only has Jonny Evans - who has signed a new one-year deal - Lisandro Martinez, Harry Maguire and Victor Lindelof as his recognised central options, although Luke Shaw can do a competent job in that role as well.
However, Shaw certainly cannot be relied upon to stay fit - Ten Hag has admitted that himself - while the long-term futures of Maguire and Lindelof remain clouded in uncertainty, as they have done for a couple of years now.
Man United letting Kambwala leave the club may suggest that they are confident of striking a deal for a replacement, as positive progress is said to have been made in their pursuit of Bayern Munich's Matthijs de Ligt.
The ex-Ajax man is said to be keen to reunite with Ten Hag at Old Trafford, but deals for Everton's Jarrad Branthwaite and Lille's Leny Yoro will prove far more complicated.
Man United announced their first signing of the summer window on Sunday, confirming the capture of talented Dutch striker Joshua Zirkzee in a £36.5m deal from Bologna.