She chided the Senate majority leader for blocking legislation passed by her chamber this year, including measures raising the minimum wage, reforming elections and expanding health care.
"We sent our legislation to the Senate," Ms Pelosi said. "Moscow Mitch says that he is the grim reaper. Imagine describing yourself as the grim reaper, that he's going to bury all this legislation."
Mr McConnell has used the term "grim reaper" to describe his role in killing what he has characterised as far-left legislation coming over from the Democrat-led House.
The Republican senator has chafed at the growing use of the nickname "Moscow Mitch". MSNBC host Joe Scarborough coined the term after Mr McConnell blocked House bills last month aimed at preventing foreign interference in US elections.
Mr McConnell described those bills as "partisan" as Senate Democrats sought to pass them by unanimous consent shortly after special counsel Robert Mueller testified that Russia was laying the groundwork to interfere in the 2020 election "as we sit here".
Asked for comment on Ms Pelosi's use of the nickname, an aide pointed to Mr McConnell's comments on the Senate floor in response to columnist Dana Milbank, who referred to Mr McConnell as a "Russian asset" around the same time.
"I don't normally take the time to respond to critics in the media when they have no clue what they're talking about, but this modern-day McCarthyism is toxic and damaging because of the way it warps our entire public discourse," Mr McConnell said during a speech in which he also defended his record of standing up to Russia.
During Ms Pelosi's remarks at the Democratic event, she also urged the Senate to pass a pair of bills approved by the House in February designed to strengthen background checks for gun buyers.
"We've been waiting since February, and now public sentiment must weigh in to save lives," the California congresswoman said.
Donald Trump had previously threatened to veto the bills, but he has expressed interest in legislation strengthening background checks in the aftermath of the mass shootings in El Paso, Texas and Dayton, Ohio.
Mr McConnell has not endorsed any specific legislation but said recently that his chamber would discuss background checks and "red-flag" legislation upon returning from the August recess. Red flag legislation makes it easier for authorities to confiscate guns of those deemed a risk to others or themselves.
Ms Pelosi did not mention Mr Trump by name but referred to him as "the person down the street" in her speech.
She accused Trump of undermining the constitution and referenced ongoing House investigations into possible obstruction of Mueller's probe into 2016 election interference and other matters.
"No one is above the law. We all must be held accountable for our actions," Pelosi said.
The Washington Post