Functional disability and chronic knee pain are frequent in combats sports participants. The McKenzie Method of Mechanical Diagnosis and Therapy (MDT) is a system for specific function examination and intervention for spinal and extremity musculoskeletal disorder. This clinical trial aimed to investigate the effectiveness of MDT, through Directional Preference, for specific function disability in Brazilian Jiu-Jitsu practitioners (BJJPs) experiencing chronic non-specific knee pain. Sixty-five BJJPs with chronic non-specific knee pain were evaluated and classified according to the MDT system. Following classification, 28 BJJPs were randomized pairwise into intervention (IG) and control (CG) groups. The procedures were consistent with the principles of DP and the intervention period was 6 weeks and follow up was included. The primary outcome was specific functional disability evaluated using the Patient Specific Function Scale (PSFS) and the secondary outcomes were pain intensity and fear-avoidance in utilizing the symptomatic limb. Data were analyzed with a two-way analysis of variance (ANOVA) and repeated measures for the outcome factor were performed (p < 0.05). For the specific functional disability, ANOVA revealed significant differences between groups based on group interaction and treatment factors (F (2, 52): 162,015; p < 0.001; η2: 0.208). The BJJPs allocated to the IG achieved significant improvements in specific functional disability, a mean difference of −4.36 (−5.01 to −3.72) post-interventional and −4.80 (−6.07 to −3.53) follow-up in the PSFS. Improvements in pain intensity and fear-avoidance were also achieved post-intervention and follow-up. Intervention in accordance with DP promoted resulted in favorable outcomes for clinical effects on specific functional disability pain intensity, and symmetry index of the lower limbs. These findings suggest that intervention based on DP may be effective in the management of chronic knee pain in BJJPs.