Using a drill at the end of its robotic arm, Curiosity bore a hole 6.4cm deep into the rock, generating powder for evaluation, Nasa said in a statement.
“The most advanced planetary robot ever designed now is a fully operating analytical laboratory on Mars,” said agency official John Grunsfeld.
“This is the biggest milestone accomplishment for the Curiosity team since the sky-crane landing last August, another proud day for America.”
The rock Curiosity targeted – described as flat and veiny– is believed to hold evidence about “long-gone wet environments”, Nasa said.
The rock has been named “John Klein” in memory of a Mars Science Laboratory deputy project manager who died in 2011.
Beforehand, however, some of the powder will be checked for contamination that may have made it onto the hardware while Curiosity was still on Earth.
Creating a tool that could handle “unpredictable” Martian rocks was no easy task, according to Nasa.
“To get to the point of making this hole in a rock on Mars, we made eight drills and bored more than 1,200 holes in 20 types of rock on Earth,” said engineer Louise Jandura.
The US$2.5 billion mission, set to last at least two years, aims to study the Martian environment to prepare for a possible future manned mission.
US President Barack Obama has set a goal of sending humans to the planet by 2030.