This study tests the hypothesis that the colonial economy of the Lambayeque region of northern coastal Peru was associated with a mechanically strenuous lifestyle among the indigenous Mochica population. To test the hypothesis, we documented the changes in the prevalence of degenerative joint disease (or DJD) in human remains from the late pre-Hispanic and colonial Lambayeque Valley Complex. Comparisons were made using multivariate odds ratios calculated across four age classes and 11 principle joint systems corresponding to 113 late pre-Hispanic and 139 postcontact adult Mochica individuals. Statistically significant patterns of elevated postcontact DJD prevalence are observed in the joint systems of the shoulder, elbow, wrist, and knee. More finely grained comparison between temporal phases indicates that increases in prevalence were focused immediately following contact in the Early/Middle Colonial period. Analysis of DJD by sex indicates postcontact males experienced greater DJD prevalence than females. Also, trends between pre- and postcontact females indicate nearly universally elevated DJD prevalence among native colonial women. Inferred altered behavioral uses of the upper body and knee are contextualized within ecological, ethnohistoric, and ethnoarchaeological frameworks and appear highly consistent with descriptions of the local postcontact economy. These patterns of DJD appear to stem from a synergism of broad, hemispheric level sociopolitical alterations, specific changes to Mochica activity and behavior, regional economic intensification, and local microenvironmental characteristics, which were all focused into these biological outcomes by the operation of a colonial Spanish political economy on the north coast of Peru from A.D. 1536 to 1751. Am J Phys Anthropol, 2009. © 2009 Wiley-Liss, Inc.