ABSTRACTInfection of individual cells by multiple virions plays critical roles in the replication and spread of many viruses, but mechanisms that control cellular coinfection during multicycle viral growth remain unclear. Here, we investigate virus-intrinsic factors that control cellular coinfection by influenza A virus (IAV). Using quantitative fluorescence to track the spread of virions from single infected cells, we identify the IAV surface protein neuraminidase (NA) as a key determinant of cellular coinfection. We map this effect to NA’s ability to deplete viral receptors from both infected and neighboring uninfected cells. In cases in which viral infectious potential is low, genetic or pharmacological inhibition of NA increases the local spread of infection by increasing the viral load received by neighboring cells. These results identify virus-intrinsic factors that contribute to cellular multiplicity of infection and suggest that optimal levels of NA activity depend on the infectious potential of the virus in question.