The classic Hanna Barbera cartoon has been transformed for the big screen with actors playing alongside a computer generated dog.
In its opening weekend the film, starring Sarah Michelle Gellar and Freddie Prinze Jr, scooped $56.7m (£38.4m) across the US and Canada, according to early estimates.
Its total gives the movie the accolade of being the biggest June opener ever, beating the three-year record set by Austin Powers: The Spy Who Shagged Me.
US and Canada top five
1. Scooby-Doo
2. The Bourne Identity
3. Windtalkers
4. The Sum of All Fears
5. Divine Secrets of the Ya-Ya Sisterhood
Spy thriller The Bourne Identity, starring Matt Damon, enters the chart at number two taking $27.5m (£18.6m).
Battlefield
John Woo's graphic war movie Windtalkers follows behind, taking a disappointing £14.5m (£9.8m) in its first week.
The movie, which sees Nicholas Cage return to the battlefield after Captain Correlli's Mandolin, cost a reported $120m (£81m) to make.
Jack Ryan thriller The Sum of All Fears, with Ben Affleck as the CIA hero, slips from the top spot to number four.
It has raked in $84.5m (£57.2m) since it was released three weeks ago.
Divine Secrets of the Ya-Ya Sisterhood falls from number two to five - taking $9.8m (£6.6m) over the three-day period.
Star Wars: Episode II - Attack of the Clones and Spider-Man continue to jostle for chart position.
Star Wars took $9.2m (£6.2m) this weekend, taking its total takings to $270.4m (£183m) and placing it at number six in the chart.
Director Sam Raimi's Spider-Man is one step behind but with total box office receipts of $389.4m (£263.5m).