COVID-19 has had a significant public health impact on both the United States and Mexico. Cross-border mobility between southern California and Mexico raises questions of transmission trends between these jurisdictions. The objective of this project was to describe binational cases amongst California US-Mexico border county COVID-19 cases and compare incidence trends to cross-border Mexico jurisdictions. Interview data from persons with confirmed SARS-CoV-2 infections in San Diego County, CA and Imperial County, CA from February to June 2020 were reviewed for binational cases; demographics and connection to COVID-19 outbreaks were assessed. Graphs of COVID-19 incidence in San Diego County and Imperial County were compared to incidence graphs in cross-border Mexico jurisdictions of Tijuana and Mexicali. Persons with COVID-19 and a binational case were older, more likely to be Hispanic, and reside in a border ZIP code than those without. Binational cases were a small proportion and tracked with overall cases during the study period. Binational cases had different trends than non-binational cases of SARS-CoV-2 in San Diego and Imperial counties from February to June 2020. Findings could inform SARS-CoV-2 mitigation strategies specific to the US-Mexico land border, particularly recommendations regarding cross-border land travel.