"If it were used correctly, it could be of real benefit, but unfortunately it's exploited for trivial matters," Sheikh Abdul Aziz al-Sheikh said on his "Fatwa" television show broadcast late Monday.
Twitter is "the source of all evil and devastation", the mufti said.
"People are rushing to it thinking it's a source of credible information but it's a source of lies and falsehood."
The social media platform is popular among both men and women in ultra-conservative Saudi Arabia, where some supported the mufti's views but many others objected.
Signup to our newsletter and follow us on Facebook and Twitter!
"This is why I will repent, and close my account to distance myself from this great evil," one Twitter user wrote with apparent sarcasm.
"Respected sheikh, how can you judge something without using it?" another post asked.
But a supporter of the sheikh wrote: "I swear the mufti has spoken the truth; the evils of Twitter are many."
Saudi Arabia adopts a strict version of Sunni Islam, including a segregation of the sexes, that influences all aspects of life in the Gulf kingdom.