In the series, Gwen Tennyson (Meagan Smith) is sent by her parents on a road trip with her Grandpa Max (Paul Eiding) and her cousin Ben (Tara Strong).

Following Ben's acquisition of the Omnitrix, the trio embark in a series of adventures, encountering various extraterrestrial and supernatural entities, including the intergalactic alien warlord overlord and conqueror Vilgax and master magician Hex (Khary Payton) and his niece Charmcaster (Kari Wahlgren), the latter of whom detects a "magical aura" within Gwen, which she begins tapping into, acquiring magic powers of her own and obtaining Charmcaster's spellbook.

On two occasions, Gwen uses the magic artifacts known as the Charms of Bezel to become the superhero Lucky Girl while becoming powerful like her cousin Ben with his Omnitrix.

Set five years after the end of the original series, Gwen Tennyson (Ashley Johnson) is now a black belt in karate, but tends to favor using her powers.

She is capable of creating energy blasts and constructs for nearly any purpose and opening up interdimensional portals, which she uses to assist Ben (Yuri Lowenthal) after Max's disappearance forces him to put the Omnitrix back on.

In the episode "Everybody Talks About the Weather", the pair's former enemy Kevin (Greg Cipes) tells Gwen her powers and abilities originate from her "alien bloodline", which she refuses to believe.

Verdona offers to take Gwen to her home planet and train her in magic, but Gwen prefers to remain on Earth with Ben and Kevin, later coming into conflict with a returned Charmcaster and Michael Morningstar, who after initially seeking to absorb her powers, seeks revenge against her after her taking back her powers reduced him to a husk.

[3][4] Set several weeks after the previous series, Gwen Tennyson, now sixteen years old, releases her dormant, inner Anodite for the second time against Zombozo (John DiMaggio) after he attempts to kill her aunt and Ben's mother Sandra (Beth Littleford), growing to a gigantic size and shouting at him to leave Ben and Kevin's families alone, terrifying him before letting him go to spread the word to all of their other enemies.

Gwen also discovers that her black-haired near-identical cousin Sunny (also voiced by Ashley Johnson) is also an Anodite and once again encounters Charmcaster and Darkstar, who are engaged in a romantic relationship after Charmcaster failed to use the Great One Dagon to resurrect her father, before helping Ben save the universe in destroying the extra and inter-dimensional demon entity and deity Dagon and his Esoterica and Lucubra.

At the end of the series finale, "A New Dawn", after travelling back in time to stop Maltruant (Mark Hamill) and watching the birth of the universe, Ben calls Gwen to get Kevin as he proposes that the trio and his partner Rook Blonko (Bumper Robinson) go on a road trip together to explore the universe that they watched being created.

When Ben finds the Omnitrix, a mysterious watch that transforms him into 10 different aliens, a world of extraterrestrial superpowers opens up to him; Gwen's identity of Lucky Girl from the previous continuity exists as a popular in-universe multimedia franchise of which she is a fan, while her enemy Kevin has a crush on her, to which she is oblivious.

[9] Gwen was originally developed to be a classmate, best friend and potential romantic interest of Ben's accompanying on his road trip with his grandfather.

[10][11] Gwen's original design, including a yellow t-shirt and ponytail, was inspired by the original design of Ben Tennyson, the red hair retained for all series, while the ponytail would be incorporated into her outfit redesign by Glen Murakami for the last season of Alien Force, the entirety of Ultimate Alien and the first season of Omniverse.

[11] Her head and hair were reworked by Glenn Wong, who also gave the character her blue top in Alien Force, while colors were added by Chris Hooten.