They are demanding protections for NSA leaker Edward Snowden.
Roughly 200 people marched to the U.S. consulate, chanting "Free Snowden" and "Arrest Obama."
Snowden is the former U.S. contractor who went public a week ago exposing a secret NSA surveillance program.
He said Washington had been hacking into Chinese computers for years.
The demonstrators consider Snowden a free-speech hero.
"We demand the whole truth be disclosed by the U.S administration, and we demand an unconditional apology by Mr. Obama," Hong Kong Legislature member Albert Ho said.
Snowden is hiding somewhere in Hong Kong in the company of supporters trying to protect him from prosecution.
He says he has no plans to leave and is prepared to face the Hong Kong justice system.