Objective Exercise is the mainstay of treatment in patients with low back pain and the first-line option in degenerative spondylolisthesis; however, there is still no consensus surrounding the superiority of any specific exercise program. Thus, the primary aim was to compare the effectiveness of lumbar stabilization exercises and flexion exercises for pain control and improvements of disability in patients with chronic low back pain and degenerative spondylolisthesis. Methods A randomized controlled trial was conducted in a tertiary public hospital and included 92 patients over the age of 50 who were randomly allocate to lumbar stabilization exercises or flexion exercises. Participants received six session of physical therapy (monthly appointments) and were instructed to execute daily at home during the six months of the study. Primary outcome (measured at baseline, one month, three months, and six months) was pain intensity (visual analog scale, from 0 to 100 mm) and disability (Oswestry Disability Index, from 0% to 100%). Secondary outcomes were disability (Roland-Morris Disability Questionnaire, from 0 to 24 points), changes in body mass index, and flexibility (fingertip to floor, in centimeters) at baseline and six months, and also the total of days of analgesic use at six-month follow-up. Results Mean differences between groups were not significant (for lumbar pain: 0.56 [95% CI = −11.48 to 12.61]; for radicular pain: −1.23 [95% CI = −14.11 to 11.64]; for ODI: −0.61 [95% CI = −6.92 to 5.69]; for Roland-Morris Disability Questionnaire: 0.53 [95% CI = −1.69 to 2.76]). Conclusions The findings from the present study reveal that flexion exercises are not inferior to and offer a similar response to stabilization exercises for the control of pain and improvements of disability in patients with chronic low back pain and degenerative spondylolisthesis. Impact statement Exercise is the mainstay of treatment in patients with chronic low back pain and degenerative spondylolisthesis, however, there is still no consensus surrounding the superiority of any specific exercise program. This study finds that flexion exercises are not inferior to and offer a similar response to stabilization exercises. Lay summary Exercise is the mainstay of treatment in patients with chronic low back pain and degenerative spondylolisthesis, but there is no consensus on the superiority of any specific exercise program. If you have DS, flexion exercises may provide similar effects to stabilization exercises.