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Abstract We analyze the CO-to-H₂conversion factor (α_CO) in the nearby barred spiral galaxy M83. We present new Hiobservations from the VLA and single-dish GBT in the disk of the galaxy, and combine them with maps of CO(1-0) integrated intensity and dust surface density from the literature.α_COand the gas-to-dust ratio (δ_GDR) are simultaneously derived in annuli of 2 kpc width fromR= 1–7 kpc. We find thatα_COandδ_GDRboth increase radially, by a factor of ∼2–3 from the center to the outskirts of the disk. The luminosity-weighted averages over the disk areα_CO= 3.14 (2.06, 4.96) $M_{\odot }{\mathrm{pc}}^{-2}{\left[\mathrm{K}\mathrm{km}{\mathrm{s}}^{-1}\right]}^{-1}$andδ_GDR= 137 (111, 182) at the 68% (1σ) confidence level. These are consistent with theα_COandδ_GDRvalues measured in the Milky Way. In addition to possible variations ofα_COdue to the radial metallicity gradient, we test the possibility of variations inα_COdue to changes in the underlying cloud populations, as a function of galactic radius. Using a truncated power-law molecular cloud CO luminosity function and an empirical power-law relation for cloud mass and luminosity, we show that the changes in the underlying cloud population may account for a factor of ∼1.5–2.0 radial change inα_CO.