Patrick Cantlay and Xander Schauffele defeated International veterans Adam Scott and Hideki Matsuyama, 6 and 5.
The Americans led for the majority of the day before a brief International resurgence on the back nine reduced the American lead to one stroke.
Each of the final four matches was 1 up through 12 holes. The Red, White, and Blue won all but one of the final matches and will go into Friday's four-ball session with a commanding 4-1 lead.
Early in the first match, Team USA's Patrick Cantlay and Xander Schauffele pounded Hideki Matsuyama and Adam Scott, 6 and 5.
The dynamic duo for the United States improved to a perfect 3-0 in foursomes at the Presidents Cup to score the first point.
The American side took five holes to make a birdie, but once the seal was broken, the US poured it on with three birdies in a row to open a 4-up lead.
Matsuyama's tee shot to 6 feet at No.10 gave the International team a chance to cut its deficit, but Scott missed the putt.