Alan Toy (Franklin Delano Roosevelt) is the first actor ever cast as Roosevelt in any professional production or filming of this musical to actually be a survivor of polio, which FDR also had. In a statement, Toy said, "It is a huge honor to join such a talented ensemble. FDR has always been a role model of accomplishment for me, and I'm thrilled to be able to play him. I tip my hat to NBC and the producers of 'Annie Live!' for authentically casting a person with a Disability for this role. I'm proud to represent the community and hope that we will continue to see more of the Disability Community in roles across entertainment media."
One of the lines spoken by Harry Connick Jr's Oliver "Daddy" Warbucks expresses a gratitude for seeing Broadway return to glory following hard times, and the audience breaks out into load applause. This is likely a nod towards the revival of Broadway following an industry-wide shutdown during the ongoing Covid pandemic.
Jane Krakowski was originally cast to play Lily St. Regis. However, in mid-November 2021, NBC announced that she would be unable to play the role because she had a breakthrough COVID case (despite being fully vaccinated), so she was replaced by fellow Broadway star Megan Hilty.
On November 24, original Broadway Annie Andrea McArdle withdrew from playing Eleanor Roosevelt to devote her energy to her recently hospitalized father. The character does not appear in the stage version of the musical but was seen in the 1982 feature film where she was played by Lois de Banzie.
Tituss Burgess is the first African American to play Rooster Hannigan.