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SARS-CoV-2 has the ability to form large multi-nucleated cells known as syncytia. Little is known about how syncytia affect the dynamics of the infection or severity of the disease. In this manuscript, we extend a mathematical model of cell–cell fusion assays to estimate both the syncytia formation rate and the average duration of the fusion phase for five strains of SARS-CoV-2. We find that the original Wuhan strain has the slowest rate of syncytia formation (6. 4 × 1 0 − 4 / h), but takes only 4.0 h to complete the fusion process, while the Alpha strain has the fastest rate of syncytia formation (0.36 /h), but takes 7.6 h to complete the fusion process. The Beta strain also has a fairly fast syncytia formation rate (9. 7 × 1 0 − 2 / h), and takes the longest to complete fusion (8.4 h). The D614G strain has a fairly slow syncytia formation rate (2. 8 × 1 0 − 3 / h), but completes fusion in 4.0 h. Finally, the Delta strain is in the middle with a syncytia formation rate of 3. 2 × 1 0 − 2 / h and a fusing time of 6.1 h. We note that for these SARS-CoV-2 strains, there appears to be a tradeoff between the ease of forming syncytia and the speed at which they complete the fusion process. • We use mathematical models to estimate the syncytia formation rate and fusion rate of five VOCs. • Wuhan and D614G strains form syncytia slowly, but complete the fusion process quickly. • Alpha and beta strains form syncytia rapidly, but complete the fusion process slowly. • There appears to be a trade-off between ease of forming syncytia and how quickly fusion is completed. [ABSTRACT FROM AUTHOR]