Physical activity levels have been declining since the COVID-19 outbreak due to social distancing and working from home. With respect to the modifiable risk factor of work-from-home (WFH) workers’ physical inactivity, the present study seeks to develop a physical activity initiative for them during this global pandemic. Using the human-centered design (HCD) approach with the online involvement of twenty-two WFH workers, the results of this study presented the assessment and insights from the sequential HCD process regarding WFH workers’ workstation in the home environment, views on received and tracked daily physical activities during the outbreak, and feedback from a five-day live physical activity prototyping. This study discusses the systematic development of the HCD approach in designing a physical activity initiative. However, a low number of participants may limit the conclusions drawn from this research. In conclusion, the HCD approach provided an opportunity to engage WFH workers and create and design with them to promote physical activity during a pandemic. After being developed through design development, being examined through hands-on use, and tested on the target group in pandemic settings, this present study informs and provides insights to design practitioners to consider the practical design of health workers during a pandemic.