Sue Lowden, a former Nevada state senator and outgoing head of the state Republican Party, made her challenge to Harry Reid official Tuesday.
Lowden said Nevadans are weary of an out-of-control federal government.
"Higher deficits and higher taxes will not bring jobs back to Nevada," she said. "Government run and rationed health care will not improve privacy, access and affordability for Nevada patients."
She also said trillions of dollars in debt would deny future generations the opportunities Americans have enjoyed.
"This isn't a partisan problem. It's a problem brought on by an unresponsive, out-of-touch federal government."
Lowden served one term in the Nevada Senate before being defeated by Valerie Wiener, D-Las Vegas. She has been GOP state chairman for a year.
With her entry into the race, the GOP primary for the right to challenge Reid now has 10 candidates including Carson City state Sen. Mark Amodei.
Reid has only one announced Democratic opponent at this point, Edward "Mr. Clean" Hamilton.
The Democratic Party responded to Lowden's announcement by criticizing her as having a "sell out" attitude toward Yucca Mountain, not strongly opposing the dump's construction north of Las Vegas.