Environmental conditions (precipitation, temperature and soil properties) differ greatly in different regions and have dual effects on the wheat growth and nutrient release of slow-release fertilizer (SRF). Conventional fertilization methods such as the multiple-split application of urea and the one-time application of SRF may have difficulty achieving a stable and high wheat yield and nitrogen (N) efficiency in various environments. Therefore, the exploration of a rational application strategy of SRF is needed for improving wheat yield and its stability in different regions. A two-year field experiment was conducted in different regions (eight test sites per year) with five patterns: 100% N (270 kg ha−1) SRF applied pre-sowing (M1); 60% N SRF applied pre-sowing and 40% N urea applied at jointing (M2); 60% N SRF applied pre-sowing and 40% N SRF applied at re-greening (M3); M2 reducing the N rate by 15% (M4); M3 reducing the N rate by 15% (M5). The fourth-split application of urea was taken as the control (CK, 270 kg N ha−1). The results suggested that the average yield in M1 decreased by 3.65% of the CK, and the yield stability was poor. Both M2 and M3 significantly increased N efficiency, grain yield and benefit, but the stability of M3 was higher than that of M2 in different environments. Considering further improvements in wheat yield, N efficiency and profit, our results suggested that the twice-split application of SRF, which also improved the adaptability of wheat in different environments, could be recommended for wheat cultivation.