Guardiola headed to Molineux with seven senior players unavailable but his team turned in a sparkling display against opponents who beat them twice last season.
De Bruyne was City's star man, winning and converting a 20th-minute penalty before having a hand in goals for Phil Foden and Gabriel Jesus.
"Since we came back after the games for the national teams, every training session he has incredible commitment," Guardiola, who saw Raul Jimenez briefly reduce the deficit in the 78th-minute, told a post-match news conference.
"Right now he is an incredibly important player for us. He always was, but in the situation we are in right now, it is so important.
"He took an incredible penalty, he took it perfectly. Then there is the amount of assists, how he runs. He played really well, like all the team.
"He likes to play football, he doesn't feel the pressure and likes to compete at a high standard."
Ilkay Gundogan's positive test for coronavirus compounded Guardiola's selection problems heading into City's opening Premier League game of the season, with Sergio Aguero, Bernardo Silva, Joao Cancelo, Oleksandr Zinchenko and Eric Garcia all injury absentees.
Aymeric Laporte only returned to training last Friday following his own Covid-19 positive, although John Stones and new signing Nathan Ake were assured for the most part in the centre of defence.
Guardiola confirmed a team predominantly made up of academy players will launch City's bid for a fourth consecutive Carabao Cup against Bournemouth on Thursday, with Leicester City up next in the Premier League on Sunday.
"Most of them are for after the [October] international break," he said when considering when asked when the injured players might return. "After that they’ll be ready.
"Laporte is not injured but he had just one training session in two months. Eric Garcia had 16 stitches, that is why he is not here but maybe for the next game he will be fit.
"The others I think after the international break – Joao, Bernardo, Oleks and Sergio will be longer.
"This is the situation. Maybe in the next days it will change a little bit."
The strain of those considerations appeared to be weighing upon Guardiola during a largely terse briefing, but he still found time to praise Foden, who made a goalscoring return to club action after being banished from the England squad earlier this month for breaching coronavirus protocols in Iceland.
"He played really well," he added.
"Apart from scoring the goal, in the first half he was not much involved. In the second half he played incredibly well.
"Since day one he trained really well. In all the time he played with us, if we decide to play five minutes or 90 minutes it doesn’t matter.
"He has a big impact and makes great contributions to the team. Today was not an exception."