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Moore era filho de operários e nasceu com uma deformidade nos pés. Passou a primeira infância sendo submetido a sucessivas cirurgias ortopédicas. Tornou-se membro do coro da igreja e estudou música, tornando-se um talentoso pianista e organista.
Estudou música e composição na Universidade de Oxford. Durante o curso, começou a trabalhar como comediante, carreira que nunca mais abandonou e que conciliava com uma carreira de sucesso como músico de jazz. Após mudar-se para os Estados Unidos, participou de diversos filmes em Hollywood, e que o tornaram mundialmente famoso.
Em 1999 ele anunciou que sofria de uma doença degenerativa rara e sem tratamento conhecido, a paralisia supranuclear progressiva (PSP). Em 2001 recebeu a Ordem do Império Britânico. A doença já estava em estado adiantado e ele recebeu a honra em uma cadeira de rodas.
Morreu vitimado por uma pneumonia, decorrente de seu quadro neurológico.
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