Bubble coalescence plays a critical role in optimizing biological and industrial processes, impacting efficiency in areas such as fermentation, wastewater treatment, and foaming control. While the relationship between chemical structure and bubble coalescence has been thoroughly explored for inorganic ions, limited data exist on organic ions and surfactants, despite their widespread use in these industries. This study addresses this gap by investigating the effects of surfactant hydrophobicity and bubble size on coalescence behavior at a flat air–liquid interface and within a bubble column. Surface tension measurements were employed to assess surfactant hydrophobicity, while bubble size and coalescence time were analyzed to determine their respective influences. The results reveal a novel quantitative relationship between surfactant hydrophobicity and the half-coalescence inhibition concentration (HCIC), a new variable introduced in this study. This relationship demonstrates that as hydrophobicity increases, the HCIC also rises, providing a new relationship between surfactant hydrophobicity and bubble coalescence. While it is well-known that more hydrophobic molecules delay coalescence, this is the first time a direct, proportional relationship has been established with HCIC, offering a new parameter for predicting and controlling coalescence phenomena.