Semiconductor photocatalysis is an important process for various applications. However, low photocatalytic activities limit the use of current photocatalysts. Several strategies were used to increase the photocatalytic activity, such as doping with transition metals. Although some success was achieved, the mechanism of the increased photocatalytic activity is still poorly understood. Moreover, titanium dioxide is usually the only material studied in this way, whereas other semiconductors have not been explored yet. Here, the effect of iron and titanium doping on the photocatalytic activity of zinc oxide is investigated. Thus, zinc oxide samples with 19 doping ratios are synthesized and characterized. A standardized test method, described by the ISO standard 22197-2, is used to measure the activity to ensure comparability with other studies. The results show an optimal doping ratio of 0.005 and 0.002 at % for iron- and titanium-doped zinc oxide, respectively. At these concentrations, the photocatalytic activity is increased by a factor of 3.4 compared to that of undoped zinc oxide. In addition, a theoretical model that describes the origin of the optimal doping ratio is developed and elucidated.