The effect of fertilizers and manure on nutrient uptake and yield of maize (Zea mays L.)- wheat (Triticum aestivum L.) and nutrient availability in Typic Haplustept was studied during 2013-14 in a long-term field experiment initiated during kharif 1997 at the Instructional Farm of Rajasthan College of Agriculture, Udaipur. The objectives were to study effect of INM on yield, content and uptake of nitrogen, phosphorus and potash and balance of these nutrients in soil under maize – wheat cropping sequence. The highest grain yield 4023 and 5007 kg ha-1 and stover yield 5330 and 7170 kg ha-1 was recorded under 100% NPK + FYM 10 t ha-1 treatment (T9) in maize and wheat, respectively. Maximum uptake of macro (N, P, K) nutrients by maize and wheat crop was recorded under application of integrated use of chemical fertilizers along with manure i.e. T9- 100 % NPK + FYM 10 t ha-1. Integrated use of chemical fertilizers and manure increased available N, P and K content of the soil followed by 150% NPK (T11) treatment are due to higher application rates of nutrients in this treatment. These contents decreased significantly in the plot, where neither fertilizer nor manure was added. Soil enrichment with 150% NPK resulted in highest positive balance of nitrogen and phosphorus in soil and negative potassium balance was observed under all treatments.