Cyle Larin put Les Bourges in front after just seven minutes, passing Dwayne De Rosario for the all-time lead with 23 goals.
Sam Adekugbe added a second deep into second-half stoppage time to ensure the Canadians remain top of the CONCACAF table.
Despite the loss, the US remains in second place in the table following Mexico's goalless draw with Costa Rica. Canada are undefeated through ten matches and look set for their first World Cup berth since 1986.
Story of the match
Canada took an early lead as a quick counter-attack started when Kamal Miller headed an errant Matt Turner goal kick into space.
Jonathan Osorio got a touch to feed Larin, who turned a combination of Miles Robinson and Jonathan David before firing inside the far post.
The U.S. had a chance to equalize a couple of minutes later when Christian Pulisic's corner kick found Chris Richards in the box, but the center back couldn't flick his chance on target.
In the 28th minute, Gyasi Zardes saw his cross headed straight into the path of Brendan Aaronson inside the box, but his follow-up shot was blocked, and Tyler Adams' blast from long distance went well over.
Pulisic had an excellent chance to level late in the first half as he was fouled by Mark Anthony-Kaye, but the Chelsea winger put his 22-yard free-kick over the crossbar.
An even better chance came off Pulisic's corner-kick in the 43rd minute, headed on frame by Weston McKennie, but saved brilliantly by Les Bourges goalkeeper Milan Borjan.
The Stars and Stripes nearly equalized just before the hour mark. McKennie hit a line-splitting pass to find Aaronson at the top of the Canada box, but Borjan made a clean save.
Canada nearly put the match away in the 70th minute when Turner spilled David's shot into the direction of Larin, but the Stars and Stripes goalkeeper atoned quickly to push the ball away from Larin’s foot.
Paul Arriola came on as a substitute and nearly on a spectacular bicycle kick, but it sailed just wide of the frame in the waning moments.
Adekugbe put the finishing touches on the victory with a 95th-minute strike, his first goal in international competition as Canada have now taken 22 points from ten games.
Man of the match: Sam Adekugbe
He was sensational at left-back, mostly keeping the Americans attacking players in check and he made his first goal for Canada a memorable one.