The fraction of matter that is in the form of baryons or dark matter could have spatial fluctuations in the form of baryon-dark matter isocurvature fluctuations. We use big bang nucleosynthesis calculations compared with observed light element abundances as well as galaxy cluster gas fractions to constrain cosmological variations in the baryon fraction. Light element abundances constrain spatial variations to be less than 26-27%, while a sample of "relaxed" galaxy clusters shows spatial variations in gas fractions less than 8%. Larger spatial variations could cause differential screening of the primary cosmic microwave background anisotropies, leading to asymmetries in the fluctuations and ease some tension with the halo-star 7Li abundance. Fluctuations within our allowed bounds can lead to "B-mode" CMB polarization anisotropies at a non-negligible level.