Businesses have to make sufficient profits to sustain activities and grow in the long run. Profitability is important especially in manufacturing industry sector that contributes to economic growth through export, employment and innovation channels in developing countries including Turkey and is the largest subsector of industry sector. In this article main determinants at firm level of profitability have been searched with the Central Bank of the Republic of Turkey (CBRT) sectoral balance sheets which is the largest real sector data set in our country by using two-way panel data analysis in the period 1996-2015. Econometric analysis results show that in Turkish manufacturing industry sector return on assets is negatively affected by leverage ratio and tangible assets to total assets ratio and positively affected by accounts receivables turnover and real volume of assets. According to results of analysis businesses wanting to increase profitability should use less debt, enhance efficiency of tangible assets and collect receivables without decreasing sales. The rise of general profitability level in manufacturing industry is going to boost economic growth and development.