Provided are a computer program product, system, and method for synchronous mode replication to multiple clusters receiving a write to a volume from a host. A received write is cached in a memory. A determination is made of a replication rule indicating one of a plurality of replication modes for a first cluster and a second cluster used for replication for the write, wherein one of the replication modes comprises a synchronous mode. A determination is made that the replication rule indicates a synchronous mode for the first and the second clusters. The write is transmitted from the memory to the first cluster to store in a first non-volatile storage of the first cluster and to the second cluster to store in a second non-volatile storage in response to determining that the replication rule indicates the synchronous mode.