This study was aimed to select suitable crop rotation system by exploring the effect of the different crop rotation systems on soil available nutrients and wheat yield in Fluvo-aquic soil in Huang-Huai Plain. A field experiment was conducted with five treatments:(1) continuous annual wheat-maize (WM-WM-WM), (2) annual wheat-maize+annual wheat-soybean alternately (WM-WS-WM), (3) annual wheat- maize+annual wheat-peanut (WM-WP-WM), (4) continuous annual wheat-peanut (WP-WP-WP), (5) continuous annual wheat-soybean (WS-WS-WS). The results showed soil available nutrients decreased generally with soil depth under all treatments. The different of alkali-hydrolyzed nitrogen (AN) content in different soil layers was higher with time among treatments. The AN contents in 0-20 cm soil layer under WM-WP-WM and WP-WP-WP were higher. The nitrate nitrogen (NO₃^--N) and ammonium nitrogen (NH₄⁺-N) contents in 0-20 cm under WP-WP-WP and WS-WS-WS were higher, and with the highest as 43.98 mg/kg and 17.58 mg/kg under WP-WP-WP. The available phosphorus (AP) content and available potassium content under WP-WP-WP were higher, with the highest value as 24.49 mg/kg and 172.80 mg/kg, respectively. Both crop rotation system and soil depth affected NO₃^--N, NH₄⁺-N, AN, AP and AK. The grain protein content of wheat under WP-WP-WP changed significantly with time, with the highest value as 17.83%. The highest wheat biomass and yield were found under WP-WP-WP and WS-WS-WS. Moreover, there was a positive correlation between wheat N harvest index and wheat harvest index. The WP-WP-WP treatment increased the number of grains (34.2/ear), and the WS-WS-WS treatment increased the number of wheat (267 000 ears/hm²). During the experimental period, in the Fluvo-aquic soil in Huang-Huai Plain, the contents of soil AN, NO₃^--N, NH₄⁺-N, AP, above ground biomass and grain protein were increased under WP-WP-WP. The NH₄⁺-N content was increased under WS-WS-WS. Meanwhile, the highest wheat yield was obtained under WS-WS-WS and WP-WP-WP. Therefore, the wheat-peanut and wheat-soybean rotation models were suggested as the optimum crop rotation system in this area.