Octanol–water partition coefficients (log K_ow) are widely used in pharmaceutical and environmental chemistry to assess the lipophilicity of compounds. Traditionally log K_ow is determined using a shake-flask method that uses milliliters of sample and solvent and requires hours for preparation, extraction, and analysis. Here, we report an automated system for rapid log K_ow determination for an array of compounds using slug flow nanoextraction (SFNE) enabled by a microfluidic chip. In the method, an autosampler is used to introduce 1 μL of sample into a microfluidic device that segments the injected volume into a series of 4 nL slugs that are each paired to an adjacent octanol slug. Each octanol–water phase pair is compartmentalized by an immiscible fluorous carrier fluid. During flow, rapid extraction occurs at each octanol–water interface. The resulting linear array of slugs flows into an online UV absorbance detector that is used to determine concentrations in the phases, allowing the log K_ow to be measured. The microfluidic device allows toggling between two-phase “aqueous plug” generation (aqueous sample separated by fluorous carrier fluid) and three-phase “phase pair” generation. In this way, online calibration for detection in the aqueous phase can be achieved. The method is applied to determining log K_ow for a panel of seven pharmaceutical compounds, including complete calibration curves, at three different pHs in under 2 h using 5 μL of extraction standard and 2.9 μL of octanol per extraction standard analyzed.