Phototherapy with low-level laser therapy (LLLT) and light-emitting diode therapy (LEDT) has arisen as an interesting alternative to drugs in treatments of musculoskeletal disorders. However, there is a lack of studies investigating the effects of combined use of different wavelengths from different light sources like lasers and light-emitting diodes (LEDs) in skeletal muscle disorders. With this perspective in mind, this study aimed to investigate the effects of phototherapy with combination of different light sources on nonspecific knee pain. It was performed a randomized, placebo-controlled, double-blinded clinical trial. Eighty-six patients rated 30 or greater on the pain visual analogue scale (VAS) were recruited and included in study. Patients of LLLT group received 12 treatments with active phototherapy (with 905 nm super-pulsed laser and 875 and 640 nm LEDs, Manufactured by Multi Radiance Medical, Solon, OH, USA) and conventional treatment (physical therapy or chiropractic care), and patients of placebo group were treated at same way but with placebo phototherapy device. Pain assessments (VAS) were performed at baseline, 4th, 7th, and 10th treatments, after the completion of treatments and at 1-month follow-up visit. Quality of life assessments (SF-36®) were performed at baseline, after the completion of treatments and at 1-month follow-up visit. Our results demonstrate that phototherapy significantly decreased pain (p < 0.05) from 10th treatment to follow-up assessments and significantly improved (p < 0.05) SF-36® physical component summary at posttreatments and follow-up assessments compared to placebo. We conclude that combination of super-pulsed laser, red and infrared LEDs is effective to decrease pain and improve quality of life in patients with knee pain.