Deep-space network channels are characterized “in part” by asymmetric channel rates. The effect of the asymmetric channel rates is that the slow acknowledgement (ACK) channel cannot effectively support transmission of the ACK segments generated at the data receiver. Increment of data block size and extension of the retransmission timeout (RTO) timer are widely used transmission mechanisms for eliminating the effect of highly channel-rate asymmetry. The aggregate custody signal (ACS) is recently proposed to resolve the effect of asymmetric channel rates in deep-space networks. In this article, these three acknowledgment mechanisms are studied, with a focus on a comparison of their effectiveness evaluation over highly asymmetric deep-space network channels accompanied by data loss. The study is conducted through realistic file delivery via an experimental testbed infrastructure. It is found that the ACS mechanism shows significant performance advantages over other two mechanisms for both the “normalized” goodput and total data amount in successful file delivery. In particular, the ACS mechanism makes it a better choice to operate with small data bundles without increasing the RTO timer length.