This prospective randomized controlled trial aimed to investigate the impact of early postoperative sequential motor control (starting first day post-operatively) and core stabilization training (starting fifth week post-operatively) compared to conventional exercise (starting fifth weeks post-operatively) on the risk of developing persistent spinal pain syndrome type-2 (PSPS-T2). 395 patients with lumbar degenerative diseases (LDDs) undergoing modified transforaminal lumbar interbody fusion and a 12-week postoperative exercise program (sequential vs. conventional exercise: 214 vs. 181) were evaluated for low back pain (LBP) intensity, Oswestry Disability Index (ODI), pressure pain threshold (PPT), temporal summation (TS), fatty infiltration of paraspinal muscles, transversus abdominis (TrA) activation capacity and Fear-Avoidance Beliefs Questionnaire (FABQ) pre-operatively, 3 months post-operatively, and 1 year post-operatively. At 3-month postoperative assessment, LBP in sequential exercise group were lower than those in conventional exercise group (P < 0.05), and sequential-exercise patients had greater local-area PPTs, lower TS, lower TrA activation capacities and less fatty infiltration of erector spinae than did the conventional-exercise patients (P < 0.05). At 1-year postoperative assessment, fewer sequential-exercise patients had PSPS-T2 compared with conventional-exercise patients (11/214 vs. 20/181; P < 0.05). LBP at rest and FABQ were lower in sequential-exercise patients than conventional-exercise patients (P < 0.05). Furthermore, both PPT and TS at 1-year postoperative assessment were associated with these measurements at 3-month postoperative assessment in patients with PSPS-T2 (P < 0.05). Postoperative sequential exercise has more positive effects to avoid PSPS-T2 than conventional exercise in patients with LDDs possibly because of its advantages in improving central and peripheral sensitization.