The animated film featuring the voice of Adam Sandler easily broke the $35.6 million September box office record set by "Sweet Home Alabama."
Sci-fi thriller Looper also had a strong start at the box office with $21.2 million.
"End of Watch" came in third at the box office this weekend with $8 million; "Trouble with the Curve" was fourth with $7.5 million and "House at the End of the Street" rounded out the top five with $7.2 million. "Pitch Perfect" debuted in sixth place with $5.2 million.
All studio estimates of gross U.S. receipts are via Box Office Mojo.
"Finding Nemo (3D)" was seventh with $4.06 million; "Resident Evil: Retribution" was eighth with $3 million; "The Master" was ninth with $2.745 million and "Won't Back Down" debuted in tenth with $2.7 million.