- Acting for Two: Yuri Lowenthal plays Mylo and the member of Deckard's gang Mylo fights in episode 1.
- Blooper: In episode 5, Vi removes her jacket to fight Sevika, leaving it on the ground in an alley. By the end of the fight, things have moved to the street, and after it's done Vi regains her jacket without going back for it.
- Celebrity Voice Actor:
- The three female leads are voiced by well known celebrities. Hailee Steinfeld voices Vi, Ella Purnell voices Jinx, and Katie Leung voices Caitlyn.
- Miyavi voices Finn.
- Completely Different Title: In Chinese - Hero League: Battle of Two Cities ("Hero League" is the Chinese translation for League of Legends).
- Creator's Oddball: For Writer/Exectutive Producer Ash Brannon. He's well known for directing Toy Story 2 and Surf's Up, both of which are kids films. This is the first adult animated series that he's written for.
- Development Gag: One of the earliest proof of concept videos for the series was a fight between Jayce and Vi. In "The Monster You Created", the two nearly come to blows, but ultimately stand down without fighting.
- Dueling Works: Just like how the original game is rivals with Dota 2, this show had its own rivalry with Dota's animated adaptation, DOTA: Dragon's Blood. And just like the game counterparts, Arcane has the advantage on popularity and publicity.
- Fake American: Ella Purnell is English, but voices Jinx with an American accent.
- Fake Brit: Katie Leung is Scottish, having grown up mostly in the Glasgow area, but affects an upper-class English accent to voice Caitlyn.
- Multiple Languages, Same Voice Actor: Finn is voiced by Miyavi in both English and the Japanese dub.
- The Other Darrin: For the original English recordings at least (foreign dubs are a different story), almost none of the characters that were originally champions in League of Legends share voice actors with their video game counterparts — the sole English Role Reprise is Reed Shannon as Ekko, and even he had only taken up the role in Legends of Runeterra just a few months before Arcane (prior to 2021, Ekko was voiced in League by Antony Del Rio).
- Playing Against Type:
- Josh Keaton, usually known for playing idealistic young heroes like Anduin Wrynn and Lann, plays the unscrupulous (and later monstrous) street thug Deckard.
- Roger Craig Smith, the voice of Sonic the Hedgehog and other badasses like Batman and Captain America, voices the mild-mannered and soft-spoken Claggor.
- In the Swedish dub, Jinx is voiced by Mimmi Sandén, whose most prominent character type are Genki Girls like Anna and Poppy, and not Ax-Crazy Jerkasses.
- Release Date Change: When first announced in 2019, Riot initially was aiming for a late 2020 release date, but thanks to complications from the COVID-19 pandemic, it had to be delayed for an extra year.
- Role Reprise: In contrast to the English recording recasting almost all of the cast for preexisting champions, many foreign dubs brought back their respective voice actors, especially for Vi and Jinx:
- Latin American Spanish dub: Romina Marroquín Payró (Vi) and Karla Falcón (teenage Jinx)
- European Spanish dub: Adelaida López (Vi) and Isatxa Mengíbar (teenage Jinx)
- Japanese dub: Yuu Kobayashi (Vi) and Sumire Uesaka (teenage Jinx), Yuko Kaida (Caitlyn) and Tasuku Hatanaka (teenage Ekko)
- Brazilian Portuguese dub: Tatiane Keplmair (Vi) and and Fernanda Bullara (teenage Jinx)
- Swan Song: Babette the Yordle Madame is played by Mira Furlan, who passed away in early 2021 after recording her lines, making this her final acting role.
- Troubled Production: Mostly averted, but apparently about a third of the production time was spent just waiting for Riot corporate to approve the rest of the work.
- Word of Gay: The people behind the show have made it pretty clear on social media that they are setting up a relationship between Vi and Cait.
- You Sound Familiar: Vander, Shoola, and Benzo are voiced by JB Blanc, Mara Junot, and Fred Tatasciore respectively. Blanc is the VA for Braum, while Junot voiced post-rework Evelynn and Tastasciore voiced both Sentinel Graves and Mordekaiser in League of Legends.
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