The present studies were conducted under All India Coordinated Research Project on Long Term Fertilizer Experiment, which was commenced since, 1972. To assess the effect of 48 years (1972-73 to 2019-20) continuous application of inorganic fertilizers with or without organic manure i.e. FYM on soil fertility status of Vertisols under soybean-wheat cropping system. The results of the present study showed that the application of recommended dose of N, P and K (20:80:20 kg ha-1 to soybean and 120:80:40 kg ha-1 to wheat) with organic manure @ 5 t FYM ha-1 improved the status of available N, P and S but decline in available K. Further, the integrated use of fertilizers with organic manure enhanced the soil organic carbon contents (9.5 g kg-1) from its initial value (5.7 g ka-1). Conjoint use of FYM with 100% NPK substantially improved contribution towards sustaining the soil fertility. A declining trend (228 to 335 kg ha-1) from its initial value (370.0 kg ha-1) of available K status was also observed as a result of continuous application of fertilizer and manure; this indicates considerable mining of available K from the soil. However, the decline of K was of lower magnitude with 100% NPK + FYM and 150% NPK treatments indicating the need to raise the dose of K fertilizer application to meet the demand of crops. Further, soil available nutrients to be adversely affected due to the imbalanced use of nutrients viz., 100% NP or 100% N alone treatments. Thus, the balance use of fertilizers continuously either alone or in combination with organic manure is necessary for sustaining soil fertility and crop productivity.