It came after a joke about "mild racism" and another about the Middle East, in which he called Israel and Palestine "selfish little bitches".
Twitter reaction was swift, with one writing: "Whole new level of bad taste."
Another said: "Hoping victims of Child Molestation managed to miss the disgusting SNL monologue of #LouieCK #sodonewithim @nbcsnl #sexabusenotfunny."
And another sent a tweet direct to NBC demanding an explanation.
Author, professor and critic Dr Anthony Bradley, of New York's Kings College, took to Twitter as well.
However, others applauded the joke, which is typical of Louis CK's controversial comedy.
Louis CK has hosted SNL three times since 2012, and has been widely well-received.
Among the comedian's high profile sketches is one that confronts the taboo of "The N Word" - in which he says "n*****" and "c***".
True to form, his turn hosting Saturday Night Live was saturated with jokes about race and politics.
Closing the show, which featured Rihanna as guests performer, he also paid tribute to David Letterman, the legendary Late Show host who is retiring next week.
- Daily Mail