Protesters were filmed breaking into the Congress building as parts of the building were aflame and smoke poured out, while demonstrators threw projectiles at riot police trying to disperse the protest.
Video on social media showed flames shooting out a window in the legislative building.
We are outraged by poverty injustice the way they have stolen the publics money said psychology professor Rosa de Chavarria. "We don't see any changes, this can not continue like this", said Mauricio Ramirez, a 20-year-old university student.
The fire services have managed to put the fire out but the extent of the damage is not yet known.
Protesters were also upset by recent moves by the Supreme Court and Attorney General they saw as attempts to undermine the fight against corruption.
Discontent had been building over the 2021 budget on social media and clashes erupted during demonstrations on Friday.
A man walks past an office of the Congress building set on fire by demonstrators during a protest demanding the resignation of President Alejandro Giammattei, in Guatemala City, Guatemala November 21, 2020.
Mr Giammattei condemned the fires on his Twitter account on Saturday, writing: "Anyone who is proven to have participated in the criminal acts will be punished with the full force of the law". "But we can not allow vandalism of public or private property", he posted.
Guatemala's Congress, dominated by conservative pro-government parties, this week approved an nearly US$13 billion (S$17.47 billion) budget, the largest in the country's history.
Guatemalans were angered because members of Congress approved US$65,000 ($89,000) to pay for meals for themselves, but cut funding for coronavirus patients and human rights agencies, among other things.
A separate, peaceful, protest took place in front of the old government palace in the historic centre of the capital, not far from Congress, also urging Giammattei to resign.
The country has also recently been hit by two damaging storms, Eta and Iota.
On Friday, Vice-President Guillermo Castillo expressed his opposition to the budget and said that both he and Mr Giammattei should step down "for the good of the country".
And Mr Castillo has said he would not resign alone.
"It was a devious blow to the people because Guatemala was between natural disasters, there are signs of government corruption, clientelism in the humanitarian aid", Jordan Rodas, the country's human rights prosecutor, said.
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