Background and Objectives: Knee osteoarthritis (KO) stands as the third leading cause of disability among the elderly, causing pain, reduced quality of life, and decreased functionality. The objective of this study is to assess the effects of an active neurodynamic technique programme at home on pain, quality of life, and function among individuals with KO. Materials and Methods: Thirty-five participants (69.7% women) aged ≥50 years with KO (Kellgren–Lawrence grades I–II) performed a femoral nerve mobilization programme at home for 6–8 weeks (20 repetitions per day). Pain intensity, using the numerical rating scale (NRS), pressure pain thresholds (PPTs), central sensitization inventory (CSI), temporal assessment, pain modulation, Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 12-item Short Form Survey questionnaire (SF-12) were collected before, after the intervention, and at one, three, six, and twelve months. Results: Participants improved significantly in pain (p < 0.05), with the improvement maintained throughout the follow-up in the NRS and for at least one month in the PPT. There were also statistically significant (p < 0.05) improvements in all subscales of the KOOS, which were maintained throughout the follow-up. Improvements were also found in the CSI and CPM. Conclusions: A home-based active neurodynamic programme for the femoral nerve has been demonstrated to yield positive effects on pain and function in patients with KO.