Spain now sit seven points clear in Group F after preserving their 100 percent record as second-placed Sweden were held to a 1-1 draw by Norway.
Jadon Sancho fed Paco Alcacer for Dortmund's opener just after the break before clinching the victory and his side's first trophy since 2017 with a clinical finish.
Liverpool face Spanish side Sevilla on Sunday at Boston's Fenway Park baseball stadium in the second game of their three-match US tour.
Borussia Dortmund twice came from behind to beat defending champions Bayern Munich 3-2.
Paco Alcacer netted twice in the first half to make it eight goals in 14 Spain appearances.
Athletic Bilbao played a man down from the 74th minute, and two men down from the 80th because of red cards in a drama-filled first-leg match against Barcelona in the Copa del Rey round of 16
Five different scorers helped Spain bring down Macedonia in a 5-1 contest.