<p>The co-nonsolvency of polymers in binary mixtures of individually good solvents remains mechanistically controversial, despite extensive research over several decades. Recent theoretical analyses based on ternary solution thermodynamics suggest that the orientation of tie lines in the polymer solvent composition plane serves as a decisive signature to distinguish between preferential interaction-driven and solvent cosolvent attraction-driven mechanisms, yet direct experimental verification of this prediction has remained elusive. Here, we report the quantitative experimental determination of tie line orientations in a poly(<i>N</i>-isopropylacrylamide) water-methanol system through direct measurement of solvent partitioning between coexisting liquid phases. Our experimental results reveal that all measured tie lines consistently exhibit positive slopes in the polymer concentration and methanol fraction composition planes, unambiguously indicating preferential enrichment of the better solvent in the polymer-rich phase. This observation provides direct experimental evidence supporting the preferential interaction-driven mechanism and establishes tie line orientation as a robust practical experimental observable for elucidating co-nonsolvency phenomena. These findings validate theoretical predictions within the Flory-Huggins framework and bridge the gap between the mean field theory and experimental reality, offering a definitive methodology that should broadly applicable to other polymer systems exhibiting similar phase separation behavior.</p>