This study tested the potential of parametric and nonparametric regression modeling utilizing multispectral data from two different unoccupied aerial vehicles (UAVs) as a tool for the prediction of and indirect selection of grain yield (GY) in barley breeding experiments. The coefficient of determination (R2) of the nonparametric models for GY prediction ranged between 0.33 and 0.61 depending on the UAV and flight date, where the highest value was achieved with the DJI Phantom 4 Multispectral (P4M) image from 26 May (milk ripening). The parametric models performed worse than the nonparametric ones for GY prediction. Independent of the retrieval method and UAV, GY retrieval was more accurate in milk ripening than dough ripening. The leaf area index (LAI), fraction of absorbed photosynthetically active radiation (fAPAR), fraction vegetation cover (fCover), and leaf chlorophyll content (LCC) were modeled at milk ripening using nonparametric models with the P4M images. A significant effect of the genotype was found for the estimated biophysical variables, which was referred to as remotely sensed phenotypic traits (RSPTs). Measured GY heritability was lower, with a few exceptions, compared to the RSPTs, indicating that GY was more environmentally influenced than the RSPTs. The moderate to strong genetic correlation of the RSPTs to GY in the present study indicated their potential utility as an indirect selection approach to identify high-yield genotypes of winter barley.