The moral message conveyed by the poem "On His Blindness" is that God does not necessarily require our work or the exercise of our talents; it is those people who mostly willingly submit to God's will that best serve him, even if that means waiting patiently. Scholars believe that Milton wrote this poem after he had begun to go blind or perhaps after he had completely lost his sight, and in the poem, Milton seems to be grappling with how he can continue his work as a writer in service to his God despite the disability which God has seen fit to place upon him. The speaker wonders if God will continue to exact Milton's "day-labour" despite the fact that the writer is now "denied" light, he believes, by that very God.

In the latter part of the poem, Milton's speaker receives his answer, a "murmur" in his own brain, and that murmur says that God does not need the work or gifts of human beings. What God wants is for people to "bear his mild yoke," and it is in doing so—in bearing the struggles they face as a result of his will—that people "serve him best." God, the voice says, is "Kingly," and his will is done by "thousands." Some are meant to "post o'er Land and Ocean without rest," and others serve him when they "only stand and wait." There are many ways to serve God, and the suggestion is that for Milton's speaker, waiting patiently will suffice.