Lodging is one of the key limiting factors in achieving high wheat yield. The application of plant growth retardants (PGRts) is regarded as an effective practice to prevent lodging. For accurate PGRt selection and the establishment of stable, high-yield production plans, it is essential to make clear the regulation strategies for lodging resistance and yield in PGRts. Field experiments were conducted at two test sites. At the initial jointing stage of wheat, Chlormequat Chloride (CCC) or Uniconazole (S₃₃₀₇) was sprayed. Compared with the control (CK), spraying CCC or S₃₃₀₇ significantly reduced the culm lodging index (CLI) and decreased the lodging rate from 7.1% to 15.6%. CCC was more capable of adjusting plant morphology (reducing plant height and second internode length and increasing stem diameter), while S₃₃₀₇ was more effective in enhancing breaking strength. The contents of GA, IAA, and zeatin nucleoside (ZR) and the activities of lignin-related enzymes (TAL and CAD) were significantly correlated with different stem indicators and CLI. Compared with CK, the yield after spraying CCC or S₃₃₀₇ increased by 6.5% and 6.0%, respectively. CCC mainly enhanced the yield by increasing grain weight per spike and the SPAD value of leaves, while S₃₃₀₇ mainly did so by increasing the number of spikes and the effective leaf area. Moreover, carbon metabolism-related enzymes (Rubisco, SS, and SPS) were significantly positively correlated with the yield. The enzyme activity of CCC was higher at the heading stage, while that of S₃₃₀₇ was higher at the filling stage. Hence, spraying CCC or S₃₃₀₇ can significantly enhance lodging resistance and yield. The optimal PGRts should be selected based on the climate and the growth stage of the wheat.