When 21 runs in 1 ball were scored in the Greatest ODI Match of All Time - 438 Match South Africa vs Australia 2006 which is the World Record for most runs in 1 ball in Cricket History
This happened in the 48th over of the Australian innings when Roger Telemachus delivered a barrage of no-balls, coupled with hits to the boundary from Ponting and Symonds who were at the crease at that time.

After the first legal ball, the 48th over read:

4NB, 1NB, 4NB, 6NB, 2 = 21 runs from 1 ball

This is the World record of Cricket for most runs in 1 ball