Mango anthracnose is among the most severe diseases impacting mango yields and quality. While this disease can be effectively controlled through chemical means, it is vital that appropriate field efficacy and fate determination studies be conducted when applying pesticides to crops in order to appropriately gauge the ecological and health risks associated with the use of these agents. GAP field trials were conducted to explore the efficacy, dissipation, and terminal residues associated with the application of mefentrifluconazole and pyraclostrobin to mango crops in six locations throughout China. These analyses revealed that three applications of mefentrifluconazole [160 mg active ingredient (a.i.) kg-1 ] in combination with pyraclostrobin mixture achieved satisfactory disease control efficacy. To simultaneously detect mefentrifluconazole and pyraclostrobin residues on mangoes, a 'quick, easy, cheap, effective, rugged and safe' (QuEChERS) high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based approach was established. The initial mefentrifluconazole and pyraclostrobin concentrations ranged from 0.18 to 0.34 mg kg-1 , and these two compounds exhibited respective half-lives of 5.6 to 10.8 days and 5.5 to 9.0 days. At 21 days following foliage application, the terminal mefentrifluconazole and pyraclostrobin residue concentrations were 0.02-0.04 and 0.01-0.04 mg kg-1 , with these concentrations being below the maximum residue limit (MRL) established for pyraclostrobin. Both short-term [acute reference dose percent (ARfD%) 0.78-2.36% and 2.0-6.08%] and chronic [acceptable daily intake percent (ADI%) 0.08-0.47% and 0.09-0.55%] dietary intake risk assessments for mefentrifluconazole and pyraclostrobin indicated that these terminal residue concentrations are acceptable for the general population. Mefentrifluconazole and pyraclostrobin in mango was rapidly degraded following first-order kinetics models. The dietary risk of mefentrifluconazole and pyraclostrobin through mango was negligible to consumers. The application of a 400 g L-1 mefentrifluconazole-pyraclostrobin suspension concentrate mixture represents a highly efficacious fungicidal approach to controlling mango anthracnose that exhibits significant potential for development as it is easily degraded and associated with low residual concentrations after application. © 2022 Society of Chemical Industry.