The Road, McCarthy's tale of a father and son in a post-apocalyptic America, was named the best novel of the year.
He wins £10,000, as does Byron Rogers, who won in the biography category for his book about Welsh poet RS Thomas.
The University of Edinburgh has awarded the two prizes since 1919. Past winners include DH Lawrence and EM Forster.
McCarthy, 74, was not at the ceremony at the Edinburgh International Book Festival to collect the award.
The other James Tait Black fiction nominees were Sarah Waters, Ray Robinson, James Lasdun, Chimamanda Ngozi Adichie and Alice Munro.
Judge Professor Colin Nicholson, of the University of Edinburgh, said: "Each of the shortlisted authors is prize-worthy.
"But my fellow judge Roger Savage agrees with me that for imaginative impact and page-turning readability, the two winning books are both destined to become classics in their respective genres."