Sleep and autonomic nervous system functioning are important bioregulatory systems. Poor sleep and low baseline respiratory sinus arrhythmia (RSA), a measure of parasympathetic nervous system activity, are associated with externalizing behaviors and depressive symptoms in youth. Rarely, however, have measures of these systems been examined conjointly. The present study examined baseline RSA (RSA-B) as a moderator of longitudinal relations between adolescent sleep and adjustment. Participants were 256 adolescents (52% girls, 66% White/European American, 34% Black/African American) from small towns and surrounding rural communities in the southeastern United States. Sleep (minutes, efficiency, variability in minutes and efficiency) was assessed at age 15 via actigraphs across seven nights. RSA-B was derived from electrocardiogram data collected at rest. Adolescents self-reported externalizing problems and depressive symptoms at ages 15 and 17. Controlling for age 15 adjustment, findings generally demonstrated that sleep predicted age 17 adjustment particularly at higher (rather than lower) levels of RSA-B, such that adolescents with good sleep (more minutes and lower variability) and high RSA-B were at lowest risk for maladjustment. The results highlight the value of examining multiple bioregulatory processes conjointly and suggest that promoting good sleep habits and regulation of physiological arousal should support adolescent adjustment.