Throughout her various incarnations, Velma is usually portrayed as a highly intelligent young woman with highly specific interests in science (which in the Scooby and Scrappy Doo series leads her to pursue a career as a NASA research scientist) or merely being very well read on obscure fields, such as Viking writing (as in the third Scooby-Doo series The Scooby-Doo Show). In Scooby-Doo! Abracadabra-Doo, Velma is described by her younger sister Madelyn as being "born with a mystery book in her hand". Consequently, Velma is usually the one to figure out the mystery, sometimes with the help of Fred and Daphne. Velma Dinkley was inspired by the brainy Zelda Gilroy, as played by Sheila James, from the late 1950s/early 1960s American sitcom The Many Loves of Dobie Gillis.[4]

A running gag in Scooby-Doo, Where Are You! and The New Scooby-Doo Movies is Velma's severe nearsightedness and her trouble with keeping her glasses on her face (often resulting in them falling off while she is being chased by the villain).[5] Another running gag is that despite the fact that she is the smallest of the Scooby-Doo gang she can actually carry away the whole gang in her arms from a villain.

When Scooby-Doo is too afraid to volunteer to help with a mission, Velma often offers him a dog treat called a "Scooby Snack" as a bribe. She also occasionally displays a strong, take-charge personality when needed, sharply ordering Shaggy to "march!" in an early episode, and she is not above physically attacking a villain when provoked, as when she kicked The Creeper in the knee for snatching her glasses right off her face. Her catchphrases are: "Jinkies!" and "My glasses! I can't see without my glasses!" (when she accidentally loses her glasses).

Velma is the most skeptical of the four human members of Mystery Inc. and most likely to discount any paranormal explanations. This is particularly evident in the movies Scooby-Doo! and the Curse of the 13th Ghost and Scooby-Doo! Return to Zombie Island, in which she discounts ghosts and zombies (real within the context of the franchise) that could not be unmasked by claiming they must be hallucinations.