The responses of soil CO2 emission to global changes are crucial for predicting the future terrestrial carbon cycle. However, the effects of warming and nitrogen addition on soil CO2 emissions during different seasons still remains unclear. A field manipulative experiment was conducted from November 2016 to October 2017 in a semi-arid grassland on the Loess Plateau of China to study the seasonal responses of cumulative soil CO2 emission to temperature increase and nitrogen addition. Open-top chambers were used to elevate temperature and N was added as NH4NO3 at a rate of 4.42 g N m−2 yr−1.The results showed that warming significantly decreased the cumulative soil CO2 emission and soil microbial metabolic rate by 14.7% and 17.6% in the growing season, respectively, but increased both of them by 19.5% and 40.3% in the non-growing season. Nitrogen addition did not change the cumulative soil CO2 emission but decreased the soil microbial metabolic rate by 11.6% in the growing season, whereas significantly decreased the cumulative soil CO2 emission and soil microbial metabolic rate by 20.3% and 21.2% in the non-growing season. Warming significantly decreased soil pH by 1% and water content by 2.5% and 29.8% and increased inorganic nitrogen by 291.6%; while nitrogen addition significantly decreased soil pH and increased inorganic nitrogen by 183.3%. The correlation analysis showed that the decreases in soil moisture (r = 0.636, p < 0.01) and pH (r = 0.746, p < 0.01) played a major regulatory role in regulating the cumulative soil CO2 emission during the growing season, while microbial metabolic rate (r = 0.944, p < 0.01) played a dominant role during the non-growing season. These results implied that there is an urgent need to incorporate soil moisture and pH in the growing season and microbial metabolic rate in the non-growing seasons in regulating soil CO2 emission into terrestrial ecosystem process models for more accurately predicting the carbon cycle under future global changes.