• Letitia Wright as Shuri / Black Panther:
  The princess and later queen of Wakanda who designs new technology for the nation. Wright was given a larger role in the film following the death of Chadwick Boseman, who starred in previous MCU media as Shuri's older brother T'Challa / Black Panther. Wright said Shuri turns to her technology as a way to grieve T'Challa.
• Lupita Nyong'o as Nakia:
  A War Dog, an undercover spy for Wakanda, from the River Tribe. Nyong'o said Nakia has "matured" following both the Blip and the death of T'Challa, explaining that her character's "priorities have shifted and sharpened" while adding that Nakia still remains "the one you want to call when you're in trouble".
• Danai Gurira as Okoye:
  The general of the Dora Milaje, Wakanda's all-female special forces. Okoye later takes on the mantle of the Midnight Angels, along with Aneka. It is revealed in the film that Okoye's husband, W'Kabi, was imprisoned following the events of the previous film. Gurira said the film would explore "many facets" of Okoye's humanity.
• Winston Duke as M'Baku:
  A powerful warrior and leader of Wakanda's mountain tribe, the Jabari. Duke indicated that following the Jabari's involvement in the events of Avengers: Infinity War (2018) and Avengers: Endgame (2019), the tribe is no longer isolated from the rest of Wakanda. He also felt M'Baku was trying to figure "out how to move forward" in this new world for Wakanda, much like many in the real world were trying to do in regards to the COVID-19 pandemic.
• Florence Kasumba as Ayo: A member and the second-in-command who later becomes the general of the Dora Milaje after Okoye is stripped of her duties. She is romantically involved with Aneka.
• Dominique Thorne as Riri Williams:
  An MIT student and genius inventor from Chicago who creates a suit of armor that rivals the one built by Tony Stark / Iron Man. Director Ryan Coogler noted that Williams is a foil to Shuri, adding "there's a thread of similarity" between the two, but are "also very, very different", with Williams and Shuri's relationship representing a similar exploration of the "diversity of the Black experience" as T'Challa and Killmonger's relationship did in Black Panther (2018).
• Michaela Coel as Aneka:
  A Wakandan warrior and member of the Dora Milaje. Aneka later takes upon the mantle of the Midnight Angels, along with Okoye. Aneka is romantically involved with Ayo. Coel was drawn to the character being queer as in the comics, and Coogler described Aneka as "kind of a rebel".
• Tenoch Huerta Mejía as Namor:
  The king of Talokan, an ancient civilization of underwater dwelling people, who refer to him as the feathered serpent god K'uk'ulkan. Huerta said Namor decides to get involved in the surface world after T'Challa publicly reveals the truth of Wakanda at the end of the first film, which consequently puts Talokan in "jeopardy", leading Namor and his people to "take action to protect themselves". Huerta also confirmed that the character is a mutant as in the comics. Huerta called Namor an anti-hero, explaining that it was important to both him and Coogler to humanize the character by making his motivations understandable despite him having an antagonistic role in the film. Coogler was enthused to include Namor's "really unique features" from the comics, including his ankle wings and pointy ears. He also described the character as "kind of an asshole, kind of romantic, and just incredibly powerful". Huerta learned a Mayan language for the role, as well as how to swim.
• Martin Freeman as Everett K. Ross: An agent of the Central Intelligence Agency who has previous ties to Wakanda.
• Julia Louis-Dreyfus as Valentina Allegra de Fontaine: The new director of the CIA and the former wife of Ross.
• Angela Bassett as Ramonda:
  The Sovereign Queen Mother of Wakanda who is grieving the death of her son T'Challa. Bassett explained that Ramonda would be trying to balance leading her people, being a mother to Shuri, and keeping threats to Wakanda "at bay", all while grieving the death of T'Challa, which is "a lot for her to handle".

Additionally, Michael B. Jordan reprises his MCU role as N'Jadaka / Erik "Killmonger" Stevens. Isaach de Bankolé, Dorothy Steel (in her final, posthumous role), and Danny Sapani reprise their roles as the Wakandan River Tribe, Merchant Tribe, and Border Tribe elders, respectively. Connie Chiume reprises her role as Zawavari, previously the Mining Tribe Elder, but now the Elder Statesman, taking over the role held by Zuri from the first film. Mabel Cadena portrays Namor's cousin Namora, while Alex Livinalli portrays the Talokanil warrior Attuma, and María Mercedes Coroy portrays Princess Fen, Namor's mother. Lake Bell and Robert John Burke appear as Dr. Graham and Smitty, respectively, a pair of CIA officials in charge of the vibranium mining operation. Richard Schiff appears as the U.S. Secretary of State, while Kamaru Usman appears as a naval officer. Comedian Trevor Noah reprises his role from the first film as Griot, an A.I. developed by Shuri. Archive footage from previous MCU films of Boseman as T'Challa / Black Panther is used in the film's ending, with Divine Love Konadu-Sun appearing in the mid-credits scene as Toussaint, T'Challa and Nakia's son.

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