With three extra-time goals in a thrilling match, De Bruyne and substitute Romelu Lukaku gave Belgium a big lead before Julian Green closed the gap with 12 minutes to go.
"For my heart, please don't give me too many games like this," said Belgium coach Marc Wilmots, who must now get his team ready to face Messi and his Argentina teammates on Saturday.
Belgium's unyielding attacks for 90 minutes on Tuesday only highlighted the great performance of the 35-year-old Howard, but the goalkeeper's teammates finally wilted in the evening heat once extra time came.
Three minutes in, Lukaku found space on the right and passed into the centre. At first, the ball was poked out before De Bruyne gained possession. But Belgium's creative genius still had the energy for a sharp move and his low shot finally missed the yellow foot of Howard and settled inside the post.
Realizing he had finally been beaten, Howard fell back on the grass almost in slow-motion, arms and legs outstretched and eyes staring up into the darkness over the Arena Fonte Nova. The best man of the match turned out to be on the losing side.
"The levee is going to break at some point," said Howard, who plays for Everton in the Premier League.
In the 105th minute, Belgium looked like it had put the game away. De Bruyne launched Lukaku into open space on the left and the Everton striker beat his club teammate with a drive to the near post.
It wasn't over on a sticky, anxiety-ridden night, however. The Americans got late hope when Green pulled one back in the 107th minute with a sterling volley on the turn that Thibaut Courtois could only touch before he saw it fly into his net.
Suddenly, United States coach Jurgen Klinsmann started wildly shouting with flailing arms "Come on, come on," and there was a new team on the field.
With six minutes to go, the Americans almost got the equalizer. A free kick move set Clint Dempsey free in the centre with only Courtois to beat. But the Belgium keeper proved he is one of the world's best by spreading his giant body to smother the shot.
With almost no work at all in 120 minutes, Courtois turned out to be more decisive than Howard had been.
With waves of chants of "USA, USA" echoing around the 48,000-seat stadium, the reinvigorated Americans kept searching for a late goal right up until the final whistle.
It never came.