Welcome to the Wayne

• Ansi Molina (voiced by Alanna Ubach)[1] – The main protagonist. Still a newcomer to the Wayne, Ansi has lived in many different places with his family in the past. He has had few friends or social experiences as a result, and is comforted primarily by books.[2] A recent recruit to Team Timbers, he is often unfamiliar with Wayne Phenomena and needs it to be explained to him, but sometimes dislikes being treated as inexperienced by Olly and Saraline as a result. He is nonetheless loyal to them as his best friends.[3]
• Olly Timbers (voiced by Billy Lopez)[4] – A frequent source of comic relief, Olly is Ansi's best friend and Saraline's older brother. He is sunny and optimistic even when Team Timbers' lives are in danger, but despite his outgoing and silly demeanor, has proven that he can be thoughtful and intelligent when the situation calls for it. He is equipped with a grappling hook.
• Saraline Timbers (voiced by Dana Steingold)[5] – Olly's seven (later in season one, eight)-year-old[6] sister, Saraline is serious, intelligent, and skilled with gadgets, and often acts as Team Timbers' leader. She is sometimes characterized as "bossy" by her brother and Ansi as a result. Saraline often struggles with making and maintaining friendships.[6] She is not taken seriously by adults at the Wayne, who believe her to be only a "little girl". She is often equipped with an extendable claw device.[2]

• Leif Bornwell III (voiced by David Hornsby, originally portrayed by Noah Galvin)[7] – A rich and somewhat selfish resident of the Wayne who credits himself for others' actions and whom Team Timbers has difficulty tolerating, often seen riding on a segway. He and Saraline become friends due to their feelings of mutual social isolation. Leif later becomes an official member of Team Timbers.
• Wendell William Wasserman (voiced by Dana Snyder)[8] – The son of vampire hunters, Wendell seeks to capture a vampire for himself to prove that he is as capable as his parents. He is somewhat friendly with Ansi due to their shared desire to prove themselves. In his capacity as a vampire hunter, Wendell can telepathically control spoons which terrify vampires for some reason.[3] Wendell later becomes an official member of Team Timbers.
• Dennis O'Bannon (voiced by Emo Philips) - A tennis-playing rich kid who originally picked on Team Timbers until he befriended and joined Team Timbers, though he still harasses Olly out of habit.
• Goodness (voiced by Charnele Crick)[9] - A library ninja who is Clara Rhone's granddaughter, later becoming an official member of Team Timbers.
• Katherine-Alice (voiced by Kimiko Glenn) - A mute girl who joins Team Timbers, able to bring origami to life. She later gains her voice in season 2.
• Albert Molina (voiced by Alfred Molina) - Ansi's divorced father who works as a psychiatrist.
• Harvey Timbers (voiced by Richard Kind) - The father of Olly and Saraline and the husband of Olympia. He also works as a comedian.
• Olympia Timbers (voiced by Annie Potts) - The mother of Olly and Saraline and Harvey's wife.
• Yelena Bishop (voiced by Veronica Taylor, originally credited as Kathleen McInerney)[10] – Known by Team Timbers as "The Spy from Apartment 8-I", she is an operative from the Calliope organization with the designation of "Agent 31-B". She serves as the principal antagonist in the first season by using the Vampires of Glamsterdam to take control of the Wayne. Following her defeat in the season 1 finale, she is forced to play host for her superior Prismal with her mission changed to eliminate Team Timbers. In the series finale, Yelena is to be revealed is Jonah's wife.
  • Masterson (voiced by Marc Thompson)[11] – Yelena's associate in Calliope who normally carries out daily choirs for her and Prismal when not helping them in their agenda.[6]
  • Flowershirt (voiced by Robbie Sublett,[12] originally portrayed by Bill Lobley) – An associate of Yelena and Masterson before taken into vampire custody in the season one finale.
• Jonah Bishop (voiced by Carey Means,[13] originally portrayed by Korey Jackson, Spriggs Fryman as "Tony Stanza") – An intelligent archaeological professor who seems to be well-versed in Wayne Phenomena who does not take Team Timbers' efforts to investigate it seriously due to their age. Olly, in particular, seems to look up to him.[2] He is also the masked figure that Team Timbers named "Tony Stanza", whose true identity they only learned. In addition, Jonah is also revealed to be Yelena's husband in the second season.
• George the Doorman (voiced by Dave Willis,[14] originally portrayed by Bill Lobley) – The Wayne's residential doorman who often seems oblivious to the Wayne Phenomenon, but remains friendly with Team Timbers and their associates.
• Julia Wiles (voiced by Nikki M. James)[15] – A resident of the Wayne whom Ansi has a crush on,[16] Olly and Saraline eventually warming up despite their initial distrust. She is eventually revealed to be part of the Wayne's conspiracy while pretending to be a Norma.
• Clara Rhone (voiced by Harriett D. Foy)[17] – The female chief librarian who runs the Wayne's secret library called the Stanza alongside Jonah's Tony Stanza alias. She befriends Ansi when he discovers it.[2]
  • John Keats (voiced by Billy Bob Thompson) - A juvenile Squidgit that works at the Stanza and is befriended by Ansi. He was named after the English Romantic poet John Keats because he stole a book written by said author from Ansi in the first episode.
• Andrei (voiced by Andrew Rannells)[18] – A Wayne resident who is a vampire suffering from amnesia as Team Timbers helps him recover his memories throughout the course of the first season.[19] He eventually regains his memories as the Duke of Glamsterdam and leader of his people.
• The Arcsine/Annacile (voiced by Katie DiCicco) – Guardian spirit of the Wayne who is targeted by Prismal in the second season for her immense power.
• Prismal (voiced by Kevin Conroy) – Yelena's cyborg superior in the Calliope organization who serves as the main antagonist of the second season, moving into Yelena's apartment since the first season finale.

Emily Ashby of Common Sense Media gave the series 3 out of 5 stars; saying that, "Nonsensical, imaginative fun rules the day in this unpredictable animated series." But added that, "Welcome to the Wayne is best treated as a sugary-treat kind of addition to kids' media diets since the content is more about garnering laughs than it is about anything outright educational."[20]