Convalescent plasma (CP) and monoclonal antibodies (mAbs), two approaches being evaluated for COVID-19 therapy, are vulnerable to antibody-resistance mutations in SARS-CoV-2 that maintain viral fitness. This preprint describes the use of replication-competent chimeric viruses to generate spike protein escape mutants to four CP samples and three mAbs. Viral RNA from resistant cultures was used to identify shared and treatment-specific escape mutations. The mutations identified in this study are currently found at low frequencies in sequencing databases, but this methodology could be used to monitor emerging virus variants and predict their impact on mAb treatments. These findings support the use of combination mAb regimens and the design of vaccines targeting conserved B cell and T cell epitopes to prevent mutational escape.