Fast Five took an estimated $83.6 million, putting it firmly in first place ahead of last week's box office topper Rio, which took $14.4 million.
The record-breaking opening of Fast Five makes it the highest debuting entry in the franchise so far, and Universal's biggest debut of all time.
Madea's Big Happy Family falls to third place this weekend taking $10 million, while the Robert Pattinson-led romantic drama Water for Elephants took $9.1 million.
Rounding out the top five films this weekend is Disney's teen film Prom, which opened to only $5 million.
Next weekend sees the US release of Marvel Studios' latest film Thor, which is reported to have taken around $93 million internationally so far.
This week's US box office top ten in full (studio estimates):
1. (-) Fast Five - $83,600,000
2. (1) Rio - $14,400,000
3. (2) Tyler Perry's Madea's Big Happy Family - $10,050,000
4. (3) Water for Elephants - $9,125,000
5. (-) Prom - $5,000,000
6. (-) Hoodwinked Too! - $4,100,000
7. (7) Soul Surfer - $3,300,000
8. (9) Insidious - $2,680,000
9. (4) Hop - $2,550,000
10. (10) Source Code - $2,530,000
Watch the trailer for Fast Five below: