Reducing the tillage and application of mulch are important strategies for soil and water conservation and sustainability of agricultural systems. Soil can be a source or sink for carbon (C) depending on management strategies and plays a major role in the global C cycle. These interacting practices can alter nutrient movement and availability to the crops, reduce water loss, slow down organic-matter (OM) decomposition, and thus enhance C sequestration. A 2-year field study was conducted to quantify the tillage and mulching effect on soil organic C (SOC), OM, nitrogen (N), phosphorus (P), and potassium (K) at two depths (i.e., 0–15 and 15–30 cm deep) in the soil profile and N, P, and K concentrations (g kg−1) in plant shoots at harvest on a Typic Calciargids in wheat–maize rotation. The four tillage systems used were zero tillage (ZT), minimum tillage (MT), conventional tillage (CT), and deep tillage (DT), and four mulch rates [control, 2 (M2), 4 (M4), and 6 (M6) Mg ha−1 year−1 wheat (Triticum aestivum L.) straw] were applied in combination with each tillage system, keeping recommended rates of fertilizers. There was a linear positive response of mulch application on SOC for both years, but it was more pronounced during the second year. Greater values were found in ZT and the lowest in CT at all depths, although greater SOC content was found in upper layers than in deeper ones. Greater shoot N, P, and K concentrations were found in MT, CT, and DT, whereas the lowest concentration was found in ZT. Mulch application has no effect on N, P, and K concentrations in shoots. The soil N concentration was not affected by tillage and mulch, yet greater soil N content was found at 0–15 cm than 15–30 cm deep. There was significant effect of tillage on soil P and K during one year as greater P and K concentrations were found under MT, CT, and DT compared to ZT. More N, P, K, and OM concentrations were found at 0–15 cm deep than at 15–30 cm deep during the whole study period. Mulch effect was significant on K, and significantly greater amounts were found at greater levels of mulch application. The increases in the soil OM were 34.5, 35.75, and 24% at 0–8, 8–16, and 16–24 cm deep respectively from the first year to the second year. Tillage effect on soil organic-matter content was not significant. Tillage increased grain production for both years. For the first year, 22.9 and 27% greater yields were found in CT and DT, whereas in the second year yields were 10.6, 17.9, and 57% greater, respectively, in MT, CT, and DT as compared to ZT. Grain production was increased at a result of mulch application by 12.9, 20.3, and 10.6% during the first year and 11.45, 23.74, and 10.9% during the second year as compared to control (i.e., without mulch). Results show the importance of mulch application and crop residue retention. Both can increase the SOC content and water-holding capacity, which will result in improved production and soil physical health over long and continuous use of mulch.