Mechanical weeding is an important technical means for organic and regenerative agricultural systems. Current weed control equipment has a variety of problems, such as difficulty adapting to high-stalk crops and poor operational quality. A high-clearance mid-tillage weeder (HMTW) has been developed to meet the mechanical weed control needs of high-stalk crops. The weeder mainly comprises a suspension device, a frame, parallel four-rod profiling mechanisms, weeding operation components, and depth-limiting soil-cutting devices. Based on the agronomic requirements of dryland flat planting, the overall structure of the HMTW was determined, and the weeding unit and flat shovel hoe were designed. Theoretical analysis was conducted on the depth stability of the HMTW, and an optimization mathematical model of the HMTW was established to further improve its tillage depth stability for agronomic requirements. The optimization objective was to minimize the deflection angle (∆β) of the profiling rod on a vertical plane, and the parameters of the parallel four-rod profiling mechanism were optimized. Based on the optimized structural parameters, a prototype of the HMTW was developed and evaluated. The test results show that the optimized HMTW exhibited a good weeding effect, and the tillage depth stability was within the design operating range. When the driving speed was 1.0 m/s and the tillage depth was 8 cm, the weed removal rate, seedling injury rate, seedling burial rate, and qualified rate of tillage depth were 90.8%, 3.2%, 4.1%, and 94%, respectively. The proposed HMTW successfully meets the weeding agronomic requirements of high-stalk crops for dryland farming, and the performance analysis and optimization models provide technical references for the design and development of such structures.