Graham has defended the president in recent days amid the ongoing controversy around his inflammatory comments toward four freshman Democratic congresswomen, as well as a controversial chant at one of his rallies on Wednesday night.
LuPone started her attacking by criticizing Graham for supporting the president before things took an ugly turn and she went after the Republican "on a personal note."
"Lindsey Graham you are a disgrace," LuPone tweeted. "On a personal note, why don't you just bite the bullet and come out. You might just come to your senses."
That sparked plenty of criticism on social media of the Tony-winning actress.
"Ahhh a good old fashioned homophobic joke from an icon in the gay community," journalist Yashar Ali reacted.
This isn't the first time an entertainer attacked Graham in such a fashion. Liberal comedian Chelsea Handler wrote a sexually-explicit tweet suggesting that Graham was being blackmailed by the Trump administration over his sexuality.
LuPone also blasted Sen. Rand Paul, R-Ky., for blocking a vote on the 9/11 victim compensation reauthorization bill.
"Don’t set foot in NYC. You too are a National disgrace. Maybe your neighbor had a point?" LuPone wrote, alluding to the 2017 assault Paul suffered by his neighbor.
A spokesperson for Paul earlier released a statement that read: "Senator Paul is not blocking anything," it read. "He is simply seeking to pay for it. As with any bill, Senator Paul always believes it needs to be paid for. Senator Paul is simply offering an amendment, which other senators support, to pay for this legislation."