In this paper, we propose a weighted fuzzy interpolative reasoning method for sparse fuzzy rule-based systems. It is based on a genetic algorithm (GA)-based weight-learning technique. The proposed method can deal with fuzzy rule interpolation with weighted antecedent variables. It also can deal with fuzzy rule interpolation based on polygonal membership functions and bell-shaped membership functions. We also propose a GA-based weight-learning algorithm to automatically learn the optimal weights of the antecedent variables of the fuzzy rules. Furthermore, we apply the proposed weighted fuzzy interpolative reasoning method and the proposed GA-based weight-learning algorithm to deal with the truck backer-upper control problem, the computer activity prediction problem, multivariate regression problems, and time series prediction problems. Based on statistical analysis techniques, the experimental results show that the proposed weighted fuzzy interpolative reasoning method by the use of the optimally learned weights that were obtained by the proposed GA-based weight-learning algorithm has statistically significantly smaller error rates than the existing methods.