During her emcee gig for the final evening of the Democratic National Convention, the "Veep" vet brought her signature brand of humor to the political stage as she intermittently threw shots at the President and his administration.
One particularly biting quip cited the White House's dispersal of D.C. protesters in June to allow a Bible photo op for Trump in front of a church.
"Just remember," Louis-Dreyfus said, "Joe Biden goes to church so regularly that he doesn't even need tear gas and a bunch of federalized troops to help him get there."
The former "SNL" star also had three zings in her pocket while encouraging viewers to text "vote" to the number 30330 throughout the event.
"That would be the president's golf score if he didn't cheat," she cracked, later adding it was an easy number to remember because "that's the year Donald Trump will finally release his tax returns."
And poking fun at Trump boasting about his cognitive exam results, Louis-Dreyfus explained, "30330. It's actually not that hard to remember. Watch. Person, woman, man, camera, TV, 30330. Anyone can do it."
She even took the "Apprentice" host to task acknowledging his fondness for clapping back over social media.
"Tonight I couldn't be prouder to be a loyal union member, a passionate climate activist and patriotic Democrat," she said into the camera. "Or as Donald Trump will call me in a tweet tomorrow: A washed-up, horse-faced no talent has-been that has low ratings."
"Well, with all due respect, sir, it takes one to know one."
Although it began on a more serious tone, one of Louis-Dreyfus's final burns came when she brought up her recent battle with breast cancer and the phone call she received from Biden during that time.
"His real warmth and kindness on that call -- man, I got to say, it made me cry," she confessed, before adding,"Our current president has made me cry, too. But it's never had anything to do with his warmth or kindness."