Instant active dry baker's yeast is a well-known product widely used for leavening of bread, produced by fermentation, and usually dried by hot air to 94–96% dry matter content. Multi-stage fluidized bed drying process is a commercial effective method for yeast drying. In this work, optimum operating parameters of an industrial continuous fluidized bed dryer for the production of instant active dry yeast were investigated. The dryer contained four zones separated with moving weirs. The operating conditions such as temperature, loading rate of compressed yeast granules, and hot air humidity had direct effects on both yeast activity and viability. The most important factors that affected the quality of the product were loading rate and the operational temperature in each zone on the bed. Optimization was performed for three loading rates of the feed to the dryer, using response surface methodology for the experimental design. The most significant factor was shown to be the loading rate with mean fermentation activity values of 620, 652, and 646 cm3 CO2/h for 300, 350, and 400 kg/h loading rates, respectively. The data analysis resulted in an optimal operating point at a loading rate of 350 kg/h and temperatures of zones 1, 2, 3, and 4 controlled at 33, 31, 31, and 29 °C, respectively. The best activity value was predicted as 668 ± 18 cm3 CO2/h, and confirmation experiments resulted in 660 ± 10 cm3 CO2/h. At the same operating point, the average viability of the cells was predicted as 74.8 ± 3.7% and confirmed as 76.4 ± 0.6%. Compared with the normal operating conditions at the plant, the optimization resulted in more than 12% and 27% improvement in the yeast activity and viability, respectively.