The Belgium captain stroked home a long range shot a minute before halftime to hand his side the lead after the goalkeeper was caught in no-man’s land after a defensive mix-up.
It was a cruel blow to English-born Matija Sarkic, who had kept a quick-paced Belgium attack at bay for almost the entire half with a remarkable series of saves, notably from Yannick Carrasco, who had four clear chances to open the scoring but was denied each time.
Leandro Trossard tucked away a penalty with the last kick of the game to double the scoreline at the death.
A back pass in the 44th minute forced Sarkic, who plays for Millwall, out of his box to try and clear but Lois Openda got in a challenge and the ball spilt for De Bruyne to side foot it home from distance to mark his milestone game.
Sarkic made another brilliant stop after the break as a deflected shot from Belgian debutant Maxim De Cuyper looked to be creeping into the corner but he flung a hand at it to push it around the post.
Montenegro might have snatched an equaliser on the break through Milutin Osmajic, who exposed the lack of speed of the returning 35-year-old Axel Witsel, playing his first game for Belgium since coming out of international retirement.
Osmajic’s effort on the hour mark was, however, saved by Belgium goalkeeper Koen Casteels.
Montenegro might have kept the scoreline to a respectable single strike but had a late meltdown with Milos Brnovic sent off for a second caution in the 88th minute before substitute Stefan Mugosa tripped Jeremy Doku to concede the late penalty.
Doku, Lois Openda and Trossard argued over who was to take it before the latter stuck it away.
De Bruyne went off after the first half as Belgium rung the changes in a bid to try to give as many players as possible a run out before their first game at Euro 2024.
They will have a second warm-up friendly against Luxembourg in Brussels on Saturday before heading to Germany next week.
Belgium's opening match at Euro 2024 is a Group E clash against Slovakia in Frankfurt on June 17. They also face Romania and Ukraine.
