Exposure to soils contaminated with heavy metals can pose human health risk to children through ingestion of contaminated soil. Soil properties such as soil pH, reactive Fe and Al oxide content, clay content, soil organic matter (SOM), and cation exchange capacity (CEC) can reduce contaminant bio-accessibility and exposure. In vitro bio-accessibility (%IVBA) of As and Pb in 19 soils was determined using U.S. EPA Method 1340. Soil properties reduced the bio-accessibility of As by 17–96.5% and 1.3–38.9% for Pb. For both As and Pb, bio-accessibility decreased with increasing Al and Fe oxide content. Al oxides were found to be the primary driver of As and Pb bio-accessibility. Multiple regressions with AlOx, soil pH, %clay and/or FeOx predicted %IVBA As (p < 0.001). The multiple regression including log (FeOx + AlOx) and %clay explained 63% of the variability in %IVBA Pb (p < 0.01). Fe and Al oxides were found to be important drivers of As and Pb bio-accessibility, regardless of in vitro method. These findings suggested soil pH should be used in addition to reactive oxides to predict bio-accessible As. Risk-based adjustments using soil properties for exposure via incidental ingestion should be considered for soils contaminated with As and/or Pb.