APOBEC3G (A3G) restricts HIV-1 infection by catalyzing processive CU deaminations on single-stranded (ss) DNA with marked 3’5’ deamination polarity. Here we show that A3G exists in oligomeric states whose composition is dictated primarily by interactions with DNA, with salt playing an important, yet secondary role. Directional deaminations correlate with presence of dimers, tetramers and larger oligomers observed by atomic force microscopy, and random deaminations appear to correlate mainly with monomers. The presence of a 30 nt weakly deaminated “dead” zone located at the 3’-ssDNA end implies the presence of a preferred asymmetric direction for A3G catalysis. Single-turnover reaction rates reveal a salt-dependent inhibition of C deamination toward the 3’-ssDNA region, offering a molecular basis underlying A3G deamination polarity. Presteady state analysis demonstrates rapid diffusion-limited A3G-ssDNA binding, a slower salt-dependent conformational change, possibly indicative of DNA wrapping, and long (5 to 15 min) protein-DNA complex lifetimes. We suggest that diverse A3G oligomerization modes contribute to the HIV-1 proviral DNA mutational bias.