Character strengths are durable positive attributes that contribute to well-being in life and at work. They are also hypothesized to contribute to the growth and flourishing of individuals and organizations. However, their associations with work performance and counterproductive work behaviors have rarely been studied. The present study seeks to identify character strengths most highly associated with work performance and counterproductive work behaviors and explores the role of individuals’ sense of meaning at work and work orientation in mediating these associations. An international sample (N = 686) completed the measures of strengths endorsement, work performance, counterproductive work behaviors, sense of meaning at work, and work orientation. Results pointed to perseverance as most highly associated with work performance and most negatively associated with counterproductive work behaviors. These associations were mediated by working individuals’ sense of meaning at work and perceptions of work as a career and as a calling. These findings highlight the contribution of perseverance to work performance and counterproductive behaviors, beyond the role of other character strengths, and highlight work meaningfulness and work orientation as psychological mechanisms underlying its effects.