Crop yield prediction is a critical measurement, especially in the time when parts of the world are suffering from farming issues. Yield forecasting gives an alert regarding economic trading, food production monitoring, and global food security. This research was conducted to investigate whether active optical sensors could be utilized for potato (Solanum tuberosum L.) yield prediction at the mid.le of the growing season. Three potato cultivars (Russet Burbank, Superior, and Shepody) were planted and six rates of N (0, 56, 112, 168, 224, and 280 kg ha−1), ammonium sulfate, which was replaced by ammonium nitrate in the 2nd year, were applied on 11 sites in a randomized complete block design, with four replications. Normalized difference vegetation index (NDVI) and chlorophyll index (CI) measurements were obtained weekly from the active optical sensors, GreenSeeker (GS) and Crop Circle (CC). The 168 kg N ha−1 produced the maximum potato yield. Indices measurements obtained at the 16th and 20th leaf growth stages were significantly correlated with tuber yield. Multiple regression analysis (potato yield as a dependent variable and vegetation indices, NDVI and CI, as independent variables) could make a remarkable improvement to the accuracy of the prediction model and increase the determination coefficient. The exponential and linear models showed a better fit of the data. Soil organic matter content increased the yield significantly but did not affect the prediction models. The 18th and 20th leaf growth stages are the best time to use the sensors for yield prediction.