Scooby-Doo features an emphasis placed on verbal rather than visual storytelling, and the work of the voice artists was particularly important. Don Messick, the voice of Astro the dog, Dr. Benton Quest, and Boo-Boo Bear—among others—provided the raspy, mumbling voice of Scooby-Doo. Radio dee jay Casey Kasem voiced Shaggy, young actor Frank Welker voiced Fred (which began Welker's long career in voice work), and actress Nicole Jaffe voiced Velma. Indira Stefanianna Christopherson voiced Daphne during the first season, and moved to New York City to marry and start a family before production began on the second season. As a result, Nicole Jaffe's roommate, Heather North, took over the role of Daphne.

Frank Welker and Nicole Jaffe also appeared together in the 1969 Elvis Presley film The Trouble with Girls.

The second season featured "chase scene" songs produced by La La Productions (which had originally been contracted to create the music for Josie and the Pussycats, the first of many shows made from the same mold as Scooby-Doo). These songs were written by Danny Janssen and Austin Roberts, and were performed by Roberts, who also made a new recording of the Scooby-Doo, Where Are You! theme song for the second season.

The first two episodes of the series ("What a Night for a Knight" and "A Clue for Scooby-Doo") both use unique title cards. Standardized title cards (featuring the oft-used run cycles for the Mystery, Inc. gang) are used for the other twenty-three episodes. Episodes from both seasons contained a laugh track, which was standard practice for American cartoon series during the 1960s and 1970s (a laugh track was even used in the main titles for "A Clue for Scooby-Doo"). It was removed for syndication in the 1980s. Not long after the Turner networks (TBS, TNT and Cartoon Network (United States)) began airing the show in 1994, the laugh track was reinstated in 1998.

SEASON I

1. What a Night for A Knight

2. Hassle in the Castle

3. A Clue for Scooby Doo

4. Mine Your Own Business

5. Decoy for a Dognapper

6. What the Hex Going On?

7. Never Ape an Apeman

8. Foul Play in Funland

9. The Backstage Rage

10. Bedlam in the Big Top

11. A Gaggle of Galloping Ghosts

12. Scooby Doo and a Mummy, Too

13. Which Witch is Which

14. Spooky Space Kook

15. Go Away Ghost Ship

16. A Night of Fright is no Delight

17. That's Snow Ghost

SEASON II

18. Nowhere to Hyde

19. Mystery Mask Mix-Up

20. Jeepers, It's the Creeper

21. Scooby's Night with a Frozen Fright

22. The Haunted House Hang Up

23. A Tiki Scare is No Fair

24. Who's Afraid of the Big Bad Werewolf?

25. Don't Fool With A Phantom