The coronavirus disease 2019 (COVID-19) pandemic tested the capacity of local health systems to understand and respond to changing conditions. Although data on new cases of COVID-19 were widely shared in communities, there was less information on the multisector response activities and factors associated with implementation. To address this gap, this empirical case study examined (a) the pattern of implementation of COVID-19 response activities and (b) the factors and critical events associated with both the pattern of new cases and the implementation of the local COVID-19 response. We used a participatory monitoring and evaluation system to capture, code, characterize, and communicate 580 COVID-19 response activities implemented in the city of Lawrence and Douglas County, Kansas. Collaboration across sectors including public health, medical services, city/county government, businesses, social services, public schools, and universities enabled the local public health system’s response effort. Documentation results showed the varying pattern of new COVID-19 cases and response activities over time and the factors identified as enabling or impeding the response and related new cases. Similar participatory monitoring and evaluation methods can be used by local health systems to help understand and respond to the changing conditions of COVID-19 response and recovery.