A coalition of leftist and liberal groups had called for the protest, ostensibly against the handing over of two Red Sea islands to Saudi Arabia.
But in a country where most protests are banned, the gesture was aimed more at defying what activists call the heavy-handed rule of President Abdel Fattah al-Sisi.
In the lead-up to the protest, police arrested dozens of activists over the past week, in some cases raiding their homes.
By Monday morning, police had closed off a street leading to the Journalists' Syndicate, where the protesters had announced they would gather, and deployed in force in central Cairo.
Instead about 50 activists, including leading leftist dissidents, gathered suddenly at a square in central Cairo chanting against the government.
"The level of (government) panic shows that they don't feel secure. And they believe the only option is repression," said Leila Seif, a prominent dissident whose activist son Alaa Abdel Fattah is jailed.
Shortly after she spoke, an armoured police van careered into the square, and an officer fired tear gas after a few protesters hurled rocks at them.
The protesters scattered into side streets. Police chased down people and arrested them, filling three vans with detainees, including several journalists.
Sisi and his interior minister had warned on the eve of the planned demonstrations that security forces would deal firmly with protesters.
Sisi, a former military chief, had said on Sunday: "Our responsibility is to protect security and stability."
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His Interior Minister Magdy Abdel Ghaffar warned that "the security services... will confront with extreme rigour any attempt to disturb public order".
Sisi was adulated by millions of Egyptians who opposed Islamist president Mohamed Morsi, whom the army overthrew in 2013.
Morsi's overthrow unleashed a brutal crackdown on Islamists that killed hundreds of protesters and an Islamist militant insurgency that has killed hundreds of policemen and soldiers.
The crackdown has extended to liberal and leftists activists, who hoped the handover of the Straits of Tiran islands to Riyadh earlier this month could help ignite protests against Sisi.
Several dissidents who had led the 2011 uprising against veteran president Hosni Mubarak are now in jail.
"There is diminishing support for him (Sisi) from many sectors that supported him for many reasons, ending in the sale of the islands," said Gamal Eid, a rights lawyer, in a phone interview.
After years of unrest that has decimated the economy, many Egyptians say the country needs a firm hand and they have little patience with protesters they consider troublemakers.
But there have been signs of growing discontent, which has apparently unnerved the government, said H.A Hellyer, a senior non-resident fellow at the Atlantic Council in Washington.
"The Egyptian state indicated a fear of widespread disruption today that did not pass, partly due to the crackdown authorities in Cairo engaged in," he said.
"But none of that has ended the current of dissension against authorities," he added.