"Serious health issues have recently arisen in our family, and under the circumstances, I have decided to discontinue my campaign," Cheney said in a statement Monday.
Cheney's decision to run against a fellow member of the GOP had caused discord both within the party and within her own family.
While running to the right of Enzi, Cheney clashed with her younger sister, Mary, over same-sex marriage. Mary Cheney, who is gay and married, claimed her sister had privately supported her marriage while bashing same-sex marriage in her campaign.
Cheney was also seen as an unwelcome interloper, having spent many years living in Virginia and only moving to Wyoming in 2012 to run for office. The sparsely polled primary race showed Enzi maintaining a wide lead over Cheney.
"Though this campaign stops today, my commitment to keep fighting with you and your families for the fundamental values that have made this nation and Wyoming great will never stop," she said.
Cheney has held several positions within the State Department, and after her father left office, launched the non-profit Keep America Safe and a brief tenure as a contributor to Fox News. Dick Cheney represented Wyoming in Congress for five terms before becoming the Secretary of Defense under George H.W. Bush and then vice president under George W. Bush.