There’s funny, there’s very funny, and then there’s Oh, Mary!, Cole Escola’s riotous new comedy that brings more laughs to Broadway than all the Gutenberg!s, Edelmans and Birbiglias combined. You can throw in Shucked for good measure.

Escola, low-key famous these last few years through YouTube videos, late night appearances and gigs for TV’s The Other Two and Difficult People, ups the career stakes immensely with Oh, Mary!, opening tonight at Broadway’s Lyceum Theatre. With nods and hints to Charles Busch, the late, great and forever Ridiculous Everett Quinton, the Sedaris siblings, Carol Burnett, Pee-wee Herman and Absolutely Fabulous, Escola squeezes just enough juice from their influences for a mix that is entirely fresh and not to be missed.

Following its acclaimed and sold-out Off Broadway engagement at the Lucille Lortel Theatre, Oh, Mary!, directed by Sam Pinkleton without so much as a split second wasted,...