Encountering Belgium for the first time since October 2015, League A newcomers Israel began assertively in the neutral setting of Hungary, as Anan Khalaili shot straight at Koen Casteels immediately from kick-off.
But De Bruyne soon led by example, giving Belgium the lead in the 21st minute.
Arriving inconspicuously into the penalty area, captain fantastic slammed domestic Manchester City teammate Jeremy Doku’s delicious delivery into the back of the net, leaving Israeli goalkeeper Yoav Gerafi with no chance of making a save.
Having been a starter instead of first-choice striker Romelu Lukaku, Dodi Lukebakio looked eager to impress. And he came close to doubling the Red Devils’ advantage not long after they took the lead, but saw his effort well-saved by Gerafi.
That kept Israel’s chances of a leveller alive, and they surprisingly got one in the 36th minute.
De Bruyne’s loss of possession allowed Khalaili to head home via a deflection off Timothy Castagne, and Israel’s equaliser was eventually credited as an own goal for the Fulham full-back.
Omri Gandelman’s headed goal was rightly ruled for offside in added-on time, as Israel returned to the dressing room with an added aura of confidence ahead of the second half.
But Belgium broke the designated visitors’ resolve almost immediately after the restart, as Lois Openda’s exquisite flick gave Youri Tielemans the opening to fire a stunningly-struck strike beyond Gerafi.
Openda then played another pivotal role in breaching the Israeli backline again, with Raz Shlomo’s foul in the area on the lively winger handing De Bruyne a brace on the evening, as he confidently converted the resulting penalty.
Unselfishly, despite being on a hat-trick, De Bruyne allowed Openda to take another spot-kick awarded to the Red Devils, following Sagiv Jehezkel’s unnecessary trip on the latter.
On this occasion, Gerafi guessed the right direction, remaining on the spot to prevent the RB Leipzig attacker from getting his name on the scoresheet.
The Manchester City midfield maestro would frustratingly be denied taking the match-ball home with him by a fine Gerafi save later on, but another head to head victory for Belgium sees Domenico Tedesco's side take a positive step towards bettering their fourth-place finish in the 2020/21 edition of the competition.
On the other hand, Israel now remain without a win over the Red Devils in close to 46 years.
Flashscore Man of the Match: Kevin De Bruyne (Belgium)
