Taking their place in the tournament's first quarter-final at Parc des Princes, Morocco topped Group B with two wins; the US finished second in Group A to reach the knockout stage for the first time in 24 years.
Match preview
Since finishing fourth at Sydney 2000, the United States have never made it past the group phase at any Olympic Games, but after beating Guinea 3-0 on Tuesday, they are now through to the final eight in Paris.
Knowing a win would see them progress to the quarter-finals, the US started quickly at Stade Geoffroy-Guichard, with midfielder Dorde Mihailovic curling home a fine free kick in the 14th minute.
Wolfsburg winger Kevin Paredes then added two goals either side of the break to ensure maximum points, which proved sufficient to finish runners-up in Group A.
Marko Mitrovic's side had lost their opening match against gold-medal favourites France, but going on to defeat New Zealand 4-1 and seeing off Guinea by another three-goal margin has kept them in contention for a podium place.
Having previously won only two of six warm-up friendlies earlier this year, the Americans will have to step up in class at Parc des Princes, where one of Africa's top teams await.
Shocking Argentina in their opening fixture set Morocco on the way towards the knockout rounds, which they ultimately reached by claiming a 3-0 victory over Iraq last time out.
Confirming themselves as Group B winners, the Atlas Lions went in front through Amir Richardson after 19 minutes, before striker Soufiane Rahimi netted his fourth goal of the tournament soon after.
Real Betis star Abde Ezzalzouli added a third, as Morocco restated their credentials as contenders for an Olympic medal, following on from an historic World Cup semi-final appearance at Qatar 2022.
Head coach Tarik Sektioui saw his team beaten by Ukraine after that opening win, but they are now the first Moroccan squad to get through the group stage since the Under-23 rule came into place in 1992.
Winners of last year's Under-23 Africa Cup of Nations, Morocco topped the group because of their superior head-to-head record against Argentina, setting up an intriguing contest with the USA.
Morocco Olympic Games Men's Football form:
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USA Olympic Games Men's Football form:
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Team News
Marko Mitrovic will await news about Gianluca Busio's recovery from a leg injury suffered during the group stage, after the Venezia midfielder missed USA's game against Guinea.
Maximilian Dietz and Griffin Yow made their first starts of the tournament on Tuesday, but a potential return for Busio could see the former drop out of the States' starting XI.
All three overage players - Djordje Mihailovic, Miles Robinson and Walker Zimmerman - are set to start, with the latter pair having featured together in central defence for either the senior team or the Olympic team 11 times to date, recording eight wins and just one defeat.
While Busio's clubmate in Venice, Tanner Tessmann, skippers the US side, Morocco's captain - Paris Saint-Germain star Achraf Hakimi - will play at his home stadium.
After forcing his way into the lineup following the Atlas Lions' famous win over Argentina, Abde Ezzalzouli is expected to form part of a front line led by top scorer Soufiane Rahimi, who plays his club football in the UAE with Al-Ain.
Meanwhile, at the back, Mehdi Boukamir and Bologna's Oussama El Azzouzi should again join forces in central defence.
Morocco possible starting lineup:
Mohamedi; Hakimi, Boukamir, El Azzouzi, El Ouahdi; Targhalline, El Khannouss, Richardson; Akhomach, Rahimi, Ezzalzouli
USA possible starting lineup:
Schulte; Tolkin, Zimmerman, Robinson, Harriel; Busio, Tessmann, Mihajlovic; Paredes, McGuire, Aaronson