In recent years, millions of people worldwide transitioned from working in offices to at home, sparking a rise in questions about productivity, health behaviors, and well-being while working at home. Moving forward, working both at home and at the office remains a part of many organizations. This study evaluates home and office workplaces using a comparative approach and a data-driven framework. The computational models in this study aim to predict the impact of 10 workplace spatial attributes on perceptions of comfort, work performance, and aspects of well-being, such as sense of connectedness and physical activity. A total of 614 worker survey responses from the United States and Canada were analyzed. Results indicate that perceived work performance was significantly higher at the office, while comfort and well-being were significantly higher at home. Analyses using logistic regression models reveal that temperature, noise, workstation furniture, and aesthetics were the most significant predictors of perceived work performance. Access to amenities and access to the outdoors were both significant predictors of sense of connectedness and physical activity. This study captures perceptions from an unprecedented moment in time and strives to quantify the impact of workplace spatial attributes on perceived work performance and well-being when working in more than one location. Insights from the analysis could inform the design of future work environments that optimize the benefits of home and office.