The DreamWorks animated sequel, featuring the voice talents of Ben Stiller, Chris Rock and Jada Pinkett Smith, earns north of £6 million to easily coast past Paranormal Activity's £2.5m earnings.
Taken 2, last week's chart-topper, falls down to number three with £2.2m. The Liam Neeson-led action sequel has now grossed an impressive £18.5m from UK screens since opening on October 4.
Hotel Transylvania falls two places to number four, while Looper rounds out the top five.
Tim Burton's Frankenweenie, which opened the BFI London Film Festival last week, debuts at number six with £741,683.
Elsewhere, the critically acclaimed Beasts of the Southern Wild enters the chart at number nine with £181,801.
The UK box office top ten in full:
1. (-) Madagascar 3: Europe's Most Wanted - £6,030,904
2. (-) Paranormal Activity 4 - £2,544,701
3. (1) Taken 2 - £2,264,856
4. (2) Hotel Transylvania - £1,023,722
5. (4) Looper - £781,211
6. (-) Frankenweenie - £741,683
7. (3) Sinister - £711,918
8. (5) The Perks of Being a Wallflower - £213,091
9. (-) Beasts of the Southern Wild - £181,801
10. (11) Brave - £176,827
Watch the trailer for Madagascar 3 below: