DOS does not natively support booting from USB. You may need a specialized tool like "Rufus" to format a drive as "FreeDOS" first, then manually copy the MS-DOS 6.22 files over.
You must enable Legacy Boot or CSM (Compatibility Support Module) in your BIOS. MS-DOS cannot boot on UEFI-only systems. Essential Post-Installation Tips ms dos 622 iso work
Are you trying to run this in a or on real hardware ? DOS does not natively support booting from USB
Standard MS-DOS 6.22 did not natively support CD-ROM drives during setup. Look for ISOs that include OAKCDROM.SYS or similar drivers in the CONFIG.SYS to ensure you can access the disc after booting. MS-DOS cannot boot on UEFI-only systems
Once you have your image, the process for getting it running depends on your environment. 1. In Virtual Machines (VirtualBox, VMware) Virtual machines are the easiest way to run DOS.
Choose "Other" as the OS type and "DOS" as the version.
Finding an "ISO" for MS-DOS 6.22 can be tricky because the original OS was distributed on 1.44MB floppy disks, not CD-ROMs. Most "working" ISOs you find online are actually "Bootable CD" wrappers that contain the floppy disk images.