Possible bioaccumulation of pesticides in crop produce may cause ill effects on animals and humans. Tribenuron-methyl is a new post-emergence herbicide and is highly efficient to control the broad-leaf weeds in cereals, pasture, and plantation crops. There are scarce studies on its bioefficacy, sensitivity to weeds, tolerance to wheat, and persistence in crop produce, which are important information required before recommending an herbicide for use by the farmers. Weed control efficiency of an herbicide is dose-sensitive and site/soil-specific. Tribenuron-methyl (75 % DF) was applied at 22.5 and 45.0 g a.i./ha along with the surfactant 300.12 mL/ha as a tank mixes after 30 days of sowing in wheat as post-emergence herbicide. The samples of wheat foliage, soil, and grains at harvest were processed and analyzed for residues by high-performance liquid chromatography using a UV detector at 240 nm. The study revealed that there was a significant reduction in weed population and dry matter accumulation due to tribenuron-methyl application at a higher dose (45.0 g/ha) compared to a lower dose (of 22.5 g/ha). The weed density was found to be from 16.1 to 44.3 no/m2 for application rate of 22.5 g/ha while at the 45.0 g/ha application, the weed density was 5.3–5.9 as compared to untreated control, where 184.3–120.5 no/m2 was observed. The yield varied from 4.30 to 4.80 t/ha as compared to 2.25–3.55 t/ha in unweeded control with the LSD value being 21.5–16.3 to 0.27–0.19. Residues were below detectable level (BDL, <0.005 mg/kg) of tribenuron-methyl since they were detected in wheat grains at 22.5 g a.i./ha rates. However, 0.012 μg/g residues were detected in wheat foliage at an application rate of 45.0 g a.i./ha. It can be concluded that it is safe to use tribenuron-methyl at 22.5 g a.i./ha on wheat crop as post-emergence herbicide.