Soil samples were collected at both jointing and maturing stages of maize and wheat to compare the effects of 4-year no-tillage (NT) and conventional tillage (CT) on seasonal variations of microbial biomass carbon (C), metabolic quotient, and invertase activity in a sandy loam soil in North China. Soil invertase activity significantly increased (P < 0.05) from summer to spring of the next year and then significantly decreased (P < 0.05) from spring to summer. With a delay of about 3 months, soil microbial biomass C and basal respiration altered in a similar pattern, while microbial metabolic quotient changed on the contrary. Compared with CT, the NT practice significantly increased (P < 0.05) soil organic C content, and tended to result in higher soil microbial biomass C and invertase activity, as well as lower soil microbial metabolic quotient, especially at the jointing stage of maize. Our results indicated that NT might play an important role in the improvement of soil microbial efficiency, especially at the maize seedling season.