The effects of long-term fertilization on crop yield and soil property in maize (Zea mays L.)-wheat (Triticum aestivum L.) rotation of desalinized soils are limited. A long-term fertilization experiment was established in 1996 to compare the impact of single and mixed mineral (NPK), and manure fertilization on crop yields and soil properties. The long-term application of manure (OF) and N fertilizer significantly increased crop yields by the 129 and 42% of yield increase, respectively, over other chemical fertilizer application. Nitrogen fertilizer increased soil surface nitrate nitrogen (NO 3 −-N) while not affecting soil ammonium nitrogen (NH 4 +-N). Organic fertilizer significantly increased soil organic carbon (SOC, increased 68.7%), available phosphorus (AP, 97.4%), and available potassium (AK, 68.5%) compared with chemical fertilizer application. Inorganic fertilizer application has less impact on microbial community composition than manure. A complete NPK plus manure fertilization program is recommended for desalinized soils around the Bohai Sea to maximize crop yields and improve soil fertility.