USA were bullied and outclassed 2-0 by Canada last month as they fell to their first loss to the country's rivals since 1985.
But USA secured payback thanks to a three-goal first half in Orlando on Friday – Jordan Morris, Gyasi Zardes and Aaron Long all on target.
Canada defender Steven Vitoria pulled a goal back in the 72nd minute, but Zardes restored USA's three-goal advantage late on.
The United States were without star Christian Pulisic due to a hip injury, while Michael Bradley and goalkeeper Zack Steffen also sat out the Nations League fixture.
However, it mattered little as USA struck inside two minutes through Morris, who reacted quickest after the ball fell to his feet and the Seattle Sounders forward made no mistake from close range.
Morris was in the thick of the action again in the 23rd minute, when USA broke and he received the ball on the edge of the area before slicing a cross to Zardes for a header past Milan Bojan.
Canada had some spells of possession, but they simply had no answer to USA, who made it 3-0 by the 34-minute mark after a curled free-kick found Long and the defender headed into the bottom corner of the net.
Sergino Dest, who opted to represent USA rather than Netherlands, almost made it 4-0, however, the Ajax full-back's shot flashed just wide of the post.
The second half was a tighter affair, with USA's Sebastian Lletget going closest to adding to the scoreline 10 minutes after the restart.
Brad Guzan did not have much to do throughout, until the USA keeper was forced into a fine fingertip save with 19 minutes remaining before watching Vitoria head the ball into the net moments later.
USA, though, had the final say after Zardes fired a shot past Bojan at the death at Exploria Stadium.
What does it mean? Destiny in USA's hands
Pressure was on Gregg Berhalter and his side pre-game. However, the United States ensured destiny remains in their own hands. USA's path to the knockout stage is simple – win their final match and achieve a superior goal differential over Canada, who top Group A on nine points.
Morris stars for USA
The 25-year-old has established himself on the international stage and he further showcased his all-round game against Canada. After scoring his ninth international goal, Morris produced a brilliant blend of pace and skill to tee up Zardes before half-time.
Davies unable to inspire Canada
Alphonso Davies and his team-mates made a statement against USA last time out. However, the Bayern Munich sensation was kept quiet in Florida. Davies, though, was involved in an interesting moment prior to the interval. The 19-year-old kicked the ball to himself and headed it to goalkeeper Bojan in an attempt to mask a backpass, but he was penalised and USA were awarded an indirect free-kick just outside the six-yard box.
USA are back in action away to Cuba on Tuesday, while Canada will await other results having already played their four Nations League fixtures.