"Just log on to social media for 10 seconds; it will hit you right in the face.
"People denying science; concocting elaborate, hurtful conspiracy theories about child abuse rings operating out of pizza parlours; drumming up rampant fears about undocumented immigrants Muslims, minorities, the poor; turning neighbour against neighbour and sowing division at a time when we desperately need unity."
She also delivered a barb at Mr Trump for claiming, without evidence, that his inauguration crowd was of a record size.
"Some are even denying things we see with our own eyes, like the size of crowds, and then defending themselves by talking about 'alternative facts'," Mrs Clinton said to roaring laughter.
"But this is serious business. Look at the budget that was just proposed in Washington.
"It is an attack of unimaginable cruelty on the most vulnerable among us: the youngest, the oldest, the poorest and hardworking people who need a little help to gain or hang on to a decent middle-class life ... And to top it off, it is shrouded in a trillion-dollar mathematical lie. Let's call it what it is: It's a con."
Mrs Clinton also compared Mr Trump's presidency to that of Richard Nixon, who resigned in the face of impeachment.
She implicitly linked Mr Trump's firing of Federal Bureau of Investigations director James Comey with the Watergate scandal, which unfolded after Mrs Clinton's graduation from Wellesley in 1969.
"By the way, we were furious about the past presidential election, of a man whose presidency would end in disgrace with his impeachment for obstruction of justice," Mrs Clinton said.
"After firing the person running the investigation into him at the Department of Justice."
She even went so far as to compare the Trump administration to an authoritarian regime.
"As the history majors among you here today know all too well, when people in power invent their own facts, and attack those who question them, it can mark the beginning of the end of a free society," she said.
"That is not hyperbole; it is what authoritarian regimes throughout history have done. They attempt to control reality, not just our laws and our rights and our budgets, but our thoughts and beliefs."
Mrs Clinton hinted at a return to politics, suggesting she may run for Congress.
"Some of you might wonder, well, why am I telling you all this? You don't own a cable news network, you don't control the Facebook algorithm, you aren't a member of Congress - yet," she said pointedly.
She also explained how she got over her election loss.
"You may have heard that things didn't exactly go the way I planned but, you know what, I'm doing OK," Mrs Clinton said.
"I've gotten to spend time with my family, especially my amazing grandchildren ... long walks in the woods, organising my closets, I won't lie, chardonnay helped a little too."
She ended by encouraging women and girls to take up the fight to make the world a better place.
"One of the things that gave me the most hope and joy after the election, when I really needed it, was meeting so many young people who told me that my defeat had not defeated them," she said.
Republican National Commitee chairwoman Ronna McDaniel criticised Mrs Clinton's remarks in a statement.
"Today's speech was a stark reminder why Hillary Clinton lost in 2016," she said.
"Instead of lashing out with the same partisan talking points, Hillary Clinton would be wise to look inward."
