With drives getting as big as they are nowadays whole disk defragging is rapidly becoming a thing of the past.
Splliting the drive into smaller partitions/drives would obviously help as you could defrag each partition/drive as needed.
Once you start talking terabytes rather than gigabytes it best to just defrag the files, that's what you want to do anyway to speed up read times.
There are two main aims to defragging, and they serve different purposes:
- Get each file into one piece for (slightly) quicker loading.
- Move all files into one contiguous block on the disk to free up disk space, the holy grail to some. (Actually that's consolidation not defragging, and doing it can fragment some files again if you want to 'fill-up' every cluster in the block).
There is also Free Space defragmentation (which helps prevent file fragmentation in the first place) and Smart file placement (which puts groups of related files together, again for faster loading).
You can read about them here, it's old but still relevant:
https://www.auslogics.com/en/articles/defragmentation/
So it depends on what you are aiming to do, and TBH with these multi-terabyte drives then freeing up space is not often likely to be an issue.
PS. Windows 10 does weekly automatic optimisation (defragmenting) in the background, unless you have turned it off or set it to a different schedule.