Yes, you can do it without any issue. put one host into maintenance mode and update and restart than continue with other hosts .

Keep in mind when you are going to put the host into maintenance before that you have to shutdown the host CVM properly .

Hello @hock chuan 

Important thing, After upgrading vCenter then ESXi, upgrade AOS from 6.1 to 6.5, because 6.1 will be EOL within Month. Upgrading ESXi and DRS is not enable, you have to upgrade it manually through vSphere not Nutanix. For more details:

https://portal.nutanix.com/page/documents/details?targetId=vSphere-Admin6-AOS-v6_5:vsp-node-upgrade-manual-vsphere-c.html

If DRS is not enabled, you must upgrade ESXi manually as below:

If you are upgrading all nodes in the cluster at once, shut down all guest VMs and stop the cluster with the cluster stop command.

If you are upgrading the nodes while keeping the cluster running, ensure that all nodes are up by logging on to a CVM and running the cluster status command. If any nodes are not running, start them before proceeding with the upgrade. Shut down all guest VMs on the node or migrate them to other nodes in the Nutanix cluster.

1. Disable email alerts in the web console under Email Alert Services or with the nCLI command.
   • NCLi> alerts update-alert-config enable=false
2. Run the complete NCC health check by using the health check command.
   •  ncc health_checks run_all
3. Run the cluster status command to verify that all Controller VMs are up and running, before performing a Controller VM or host shutdown or restart.
   •  cluster status
4. Place the host in the maintenance mode by using the web client.
5. Log on to the CVM with SSH and shut down the CVM
   •  cvm_shutdown -P now
6. Start the upgrade using vSphere Upgrade Guide or vCenter Update Manager VUM.