Sec-amines catalyzed two-step Mannich reaction for preparation of methacrolein from propionaldehyde and formaldehyde was more attractive than the C-4 selective oxidation route. Herein, a novel continuous fixed-bed process was developed for direct preparation of methacrolein from above stocks with catalysis of sec-amine grafted D301 resin. The effect of resin, sec-amine structure and grafting percentage on catalytic performance of the modified resin were detailed investigated and demonstrated by using FT-IR, TG-DTA, titration and solid-state NMR characterization methods before the optimal conditions were obtained. The grafting percentage of amine with abundant sec-amino groups onto D301 resin could reach 93.7% at optimal condition. With this new strategy, the yield and selectivity of methacrolein could attain 40.2% and 99.3%. In addition, the Mannich reaction step with activation energy of 66.3 kJ/mol was determined as the rate-controlling step through mechanism-based kinetic calculation.