Background: Urea fertilizer and MCPA herbicide are widely used agrochemicals in pastures. Even though urea hydrolysis impacts soil pH, potentially affecting MCPA dissipation, little is known about the effects of their co-application into the rhizosphere. Hence, we aimed to analyze the dynamics of urea transformation and MCPA dissipation when both are co-applied to the soil. Methods: A greenhouse experiment was conducted with a planted control and treatments incorporating urea and/or MCPA. Subsequently, pH changes, urea transformation into N‑NH4+ and N‑NO3−, the enzymatic activity of urease and dehydrogenase, and MCPA dissipation were monitored for 30 d. Results: Urea application induced a significant (p < 0.05) pH change, production of N‑NH4+ (from 50 and 250 mg kg−1) and N‑NO3− (from 206 to 347 mg kg−1), and urease (from 12 to 35 µmol N-NH4⁺g⁻1 h⁻1) and dehydrogenase (from 0.5 to 2.5 mg TPF g−1 h−1) activities. Urea also decelerated MCPA dissipation in the latter half of the experiment, whereas MCPA reduced urease activity when urea and herbicide were co-applied. Conclusions: Urea was the primary factor modifying the properties of the rhizosphere by stimulating the activity of microbial enzymes, shaping the pH changes during its mineralization, and decelerating MCPA dissipation. MCPA did not reduce urea mineralization but slowed urease activity, constituting an insight that requires further study.