Ride, who was 32 when she launched aboard the Space Shuttle Challenger on June 18, 1983, was with the National Aeronautics and Space Administration's space program from 1978 until 1987.
A physicist, Ride was among 8,000 people who answered an NASA newspaper advertisement seeking astronaut candidates.
During her NASA tenure, she was instrumental in developing the space shuttle's robotic arm, used to launch and retrieve satellites and vital to the famous repair effort on the Hubble Space Telescope.
After leaving NASA, Ride worked at Stanford University, became a professor of physics at the University of California-San Diego and was director of the California Space Institute.
The White House released a statement on behalf of President Obama and first lady Michelle Obama.
"Michelle and I were deeply saddened to hear about the passing of Sally Ride," the president's statement said.
"As the first American woman to travel into space, Sally was a national hero and a powerful role model. She inspired generations of young girls to reach for the stars and later fought tirelessly to help them get there by advocating for a greater focus on science and math in our schools.
"Sally's life showed us that there are no limits to what we can achieve and I have no doubt that her legacy will endure for years to come."