The dynamics of head-on collision of unequal-size droplets were experimentally and theoretically investigated, with emphasis on identifying distinct collision outcomes and interpreting the size-ratio dependence. A unified regime diagram in terms of bouncing, permanent coalescence, and separation after coalescence was identified for hydrocarbon and water droplets in the parameter space of the size ratio and a collision Weber number. Experimental results show that the transition Weber number, Web-c, that separates the bouncing and permanent coalescence regimes, weakly depends on the size ratio, while the transition Weber number, Wec-s, that separates permanent coalescence and separation regimes, significantly increases with the size ratio. A theoretical model based on energy balance and scaling analysis was developed to explain the size-ratio dependence of Wec-s. The theoretical results show good agreement with the experimental data for tetradecane and decane droplets, with a moderate discrepancy for water droplets.