Glycosphingolipids are key components of the arms race that drives Emiliania huxleyi-coccolithovirus interactions. While production of virally-encoded GSLs (vGSLs) regulates infection and is controlled by the activity of serine palmitoyltransferase (SPT), the rate-limiting enzyme in this lipid biosynthetic pathway, little is known about how SPT biochemical diversity impacts infection dynamics and influences which coccolithoviruses “win” at sea. Here, we characterize the SPT biochemical activity, vGSL production, and host-virus infection dynamics of three distinct coccolithoviruses (EhV-18, EhV-207 and EhV-99B1). vGSL production levels corresponded with enhanced virulence and rapid host demise, with EhV-207 being the most virulent and displaying the highest SPT activity and vGSL production. Moreover, early and rapid vGSL production in EhV-207 infected treatments was characterized by mostly species with tC17:0 LCBs. In contrast to what we expected based on our laboratory results, deep sequencing of samples obtained from natural coccolithovirus communities revealed that the most dominant SPT morphotypes associated with cells during infection were not those that resembled EhV-207 like sequences, indicative of a complicated host-virus infection dynamics network in the natural environment in which being a fast and deadly virus may not necessary be advantageous, as coccolithoviruses are dependent in high enough host density for infection and propagation.