This study establishes a theoretical foundation for the oxidation pathway of monovalent thallium (Tl(I)) to trivalent thallium (Tl(III)) on birnessite, which is responsible for the over million times enrichment of Tl in marine ferromanganese deposits over seawater concentration. Tl(I) oxidation occurs on vacant Mn(IV) sites located on basal planes of the birnessite layers and on the edge sites, in agreement with experiment. Two Mn(IV) atoms are reduced to Mn(III) when Tl(I) gives up two electrons in two one-electron steps with formation of an intermediate Tl(II) inner-sphere complex. Tl(I) oxidation is facilitated at pH > 4-5 by the partial hydrolysis of the Tl(III) inner-sphere product on the reactive basal and edge sites. Oxidation by O2 is thermodynamically unfavorable. Although density functional theory has predictive power for intermediate Tl(II) complex, it would be difficult to characterize as Tl(II) is highly reactive, and therefore probably short-lived. These findings provide the first atomic-scale description of the oxidation of Tl(I) by a manganese oxide and fill gaps in our understanding of global thallium sequestration in natural systems.