Objectives This study’s primary purpose was to determine if the extent of bodily pain, as evaluated with pain body diagrams, is associated with prosthetic-related activity restrictions, adjustment, and satisfaction among adults with a major unilateral lower-limb amputation. A secondary objective was to evaluate between-days, test-retest reliability for pain body diagrams among adults with lower-limb amputation. Methods Adults with a lower-limb amputation that occurred ≥1 year prior participated in an online, cross-sectional research study. Outcome measures included pain body diagrams and the Trinity Amputation and Prosthesis Experience Scales-Revised, which evaluates post-amputation activity restrictions, psychosocial adjustment, and prosthesis satisfaction. Linear regression modeling was used to evaluate associations between the number of painful body regions and prosthetic outcomes, after considering covariates (alpha ≤ 0.010). A subset of participants recompleted pain body diagrams to evaluate between-days, test-retest reliability. Results Data from 74 participants (n = 32 female; n = 42 transtibial-level; n = 27 traumatic etiology) were available. Beyond covariates (i.e., age, sex, amputation level), the total number of painful body regions was significantly associated with all Trinity Amputation and Prosthesis Experience Scales-Revised subscales (p < 0.001–0.006), with the exception of Social Adjustment (p = 0.764). The total number of painful body regions explained 14.5, 11.8, 11.6, and 7.4% of the variance in Functional Satisfaction with the Prosthesis, Adjustment to Limitation, General Adjustment, and Activity Restriction, respectively. In a subset (n = 54), test-retest reliability for total number of painful body regions per body diagrams was good [intraclass correlation coefficient (ICC) 3,1 = 0.84]. Conclusions A greater number of painful body regions is associated with greater activity restriction, worse adjustment, and lower prosthesis satisfaction, supporting the need to enhance post-amputation pain management and both amputated- and secondary-site pain prevention. Ethical committee number IRB #1611862.