Despite the widespread occurrence of axon degeneration in the injured and diseased nervous system, our understanding of axon degeneration remains incomplete. Sterile Alpha and TIR motif-containing protein 1 (SARM1) has been identified as important for regulating axon degeneration in many parts of the peripheral nervous system. The role of SARM1 in cortical axon plasticity and degeneration remains unclear. Here we use live imaging through a cranial window to directly visualise excitatory axons in the cortex of adult Thy1-GFP-M mice (WT-GFP) crossed with SARM1 null mutants (SARM1KO-GFP). Long synapse-rich axons are targeted with the imaging laser to create a microlesion, disconnecting the distal axon segment from the cell body. Imaging of the surviving axon at 48h intervals allows synapses to be identified as stable, gained, or lost (pre/post-lesion). In the absence of SARM1, synaptic density is maintained, but synaptic turnover (gains and losses) is higher in SARM1KO-GFP axons (WT-GFP:10axons; SARM1KO-GFP:10axons; p=<0.05). In disconnected axon segments undergoing Wallerian degeneration, we identify and compare key steps in the degenerative process. Preliminary analysis shows disconnected SARM1KO-GFP axons undergo axon thinning and reactive blebbing, remain intact for a period of time, and then commence similar fragmentation processes as WT-GFP axons (WT-GFP:10axons, SARM1KO-GFP:10axons). Our data highlight the key role of in vivo imaging in providing new insights on how SARM1 contributes to synaptic plasticity and axon degeneration in the injured central nervous system and open the door for targeting SARM1 in therapeutic interventions in the injured brain.