In China, the high use of nitrogen fertilization for agricultural production and intensive mono-cropping systems have adversely affected the agricultural ecosystem and environment. Therefore, to improve the sustainable agricultural production system, farming systems need to be adjusted within the country. Consequently, a two-year (2021–2022) field experiment was conducted on the maize/soybean intercropping practices with/without nitrogen (N) fertilization (i.e., N0; 0 N kg ha− 1 and N1; 225 N kg ha− 1) to know whether such cropping system can improve the nutrients uptake and crop yields, soil physio-chemical properties, and soil enzymes, which ultimately results in enhanced crop yield. The results revealed that maize intercropping treatments (i.e., N0MI and N1MI) had higher crop yield, biomass dry matter, and 1000-grain weight of maize than mono-cropping treatments (N0MM, and N1MM). Nonetheless, these parameters were optimized in N1MI treatments in both years. For instance, N1MI produced the maximum grain yield (10105 and 11705 kg ha− 1), biomass dry matter (13893 and 14093 kg ha− 1), and 1000-grain weight (420. and 449 g) of maize in the year 2021 and 2022, respectively. Conversely, soybean intercropping treatments (i.e., N0SI and N1SI) reduced such yield parameters for soybean. Also, the land equivalent ratio (LER) and land equivalent ratio for N fertilization (LERN) values were always greater than 1, showing the intercropping system's benefits in terms of yield and improved resource usage. Moreover, maize intercropping treatments (i.e., N0MI and N1MI) and soybean intercropping treatments (i.e., N0SI and N1SI) significantly (p < 0.05) enhanced the nutrient uptake (i.e., N, Fe, P, K, Ca, and Zn) of maize and soybean, however, these nutrients uptakes were more prominent in N1MI and N1SI treatments of maize and soybean, respectively in both years (2021 and 2022) compared with their mono-cropping treatments. Similarly, maize-soybean intercropping treatments (i.e., N0MSI and N1MSI) significantly (p < 0.05) improved the soil-based N, K, P, NH4, NO3, and soil organic matter, but, reduced the soil pH. Such maize-soybean intercropping treatments also improved the soil enzymatic activities such as protease (PT), sucrose (SC), acid phosphatase (AP), urease (UE), and catalase (CT) activities. This indicates that maize-soybean intercropping could potentially contribute to higher and better crop yield, enhanced plant nutrient uptake, improved soil nutrient pool, physio-chemical characteristics, and related soil enzymatic activities. Thus, preferring intercropping to mono-cropping could be a preferable choice for ecological viable agricultural development.