Manual removal of the main stem tips of cotton (Gossypium hirsutum L.) is a traditional topping approach in China. However, chemical topping has become an inevitable trend. Therefore, it is of great significance to study the effect and appropriate concentration of agents for advancement of cotton whole process mechanization management technology. A two-year field experiment was conducted to evaluate the effects of different methods of topping on cotton yield and plant architecture in Shihezi, Xinjiang, China. Plant topping included manual topping, non-topping as the control, and chemical topping (high, medium, and low concentrations of topping agent) to determine a suitable topping method and topping agent concentration for machine-picked cotton. Chemical topping was performed using fortified mepiquat chloride (DPC⁺). Chemical topping and manual topping increased seed cotton yield compared with non-topping. Compared with non-topping, high, medium, and low concentrations of topping agent significantly increased the yield by 19.5–27.9%, 24.1–29.4%, and 24.3–28.4%, respectively. Topping treatment mainly regulated yield and total boll number per unit area by affecting the boll number per plant and had a certain positive effect on fiber strength but no significant effect on boll weight. Chemical topping affected both vertical and horizontal plant architecture characteristics of cotton; the plant height of low-, medium-, and high-concentration treatments increased by 7.2–11.4 cm, 4.0–5.7 cm, and 2.3–4.4 cm, respectively, compared with manual topping and decreased by 5.1–7.8 cm, 8.3–13.5 cm, and 9.4–16.9 cm, respectively, compared with non-topping. The number of main stem internodes was significantly different between high- and low-concentration treatments, which showed that the higher the concentration, the lower the number of the main stem internodes. Chemical topping controlled the increase in the length of the upper branches, the higher the concentration, the lower the increase in the length of the upper fruit branch. Compared with non-topping, the medium concentration of topping agent controlled the number of fruit branches, similar to manual topping. The role of upper internode length of cotton cannot be ignored under chemical topping. The peak leaf area index (LAI) of medium- and high-concentration treatments was delayed for 1 week in the late growth period (after topping for 28 d) compared with manual topping. The LAI values were high, and the duration of high values was prolonged. The optimal chemical topping agent was the medium concentration.