His wife Kathryn Adams announced his death on his radio show on Wednesday. He had been suffering from lung cancer.
Best known as the host of the long-running talk radio programme The Rush Limbaugh Show, he was a towering figure in the conservative movement for years.
Three presidents appeared on his show, and he received the US Presidential Medal of Freedom in 2020.
But he was as controversial as he was influential, accused of voicing racist, sexist and homophobic views throughout his career.
The climate change denier peddled numerous conspiracy theories on the air, staunchly opposed immigration, and was a hard-line advocate for US exceptionalism.
He was also a vocal supporter of President Donald Trump, who in 2020 bestowed on Limbaugh the Medal of Freedom - the highest US civilian honour.
Speaking on Fox News after Limbaugh's death, Mr Trump called the radio host "irreplaceable".
Born in Missouri on 12 January 1951, Limbaugh first began working in radio at his local station when he was in high school. After graduating in 1969, he started at Southeast Missouri State University but dropped out after two semesters and took his first job at a music radio station in Pennsylvania.
Limbaugh initially struggled to succeed in broadcasting. He was fired from his first two jobs and moved back in with his parents in Missouri. He became the host of a public affairs talk show in Kansas City, but again lost his position.
In 1979, he began working for the Kansas City Royals baseball team. During this time he took trips to Europe and Asia, experiences Limbaugh later said reinforced his belief in US exceptionalism.
"I go to Europe and say, 'Wait a minute. Why is this bedroom so damned old-fashion and doesn't work? What the hell is this? They call this a toilet?' So I started asking myself: 'How is it that we, who have only been around 200 years, are light-years ahead of people that have been alive a thousand?'" he told his listeners in 2013.
Limbaugh returned to radio in 1983, launching The Rush Limbaugh Show the following year at California's KFBK radio station.
But the outspoken conservative only began to find widespread success after the Federal Communications Commission (FCC) repealed its fairness doctrine in 1987 - a regulation requiring US broadcasters to present both sides of a controversial opinion. As the Wall Street Journal put it in 2005, this decision led to "hyper-articulate conservative hosts opening their microphones to millions of hyper-angry conservative voters".
In 1988 the show became nationally syndicated, broadcast live on hundreds of radio stations around the country. By 2020, it attracted around 27 million listeners each week.
The programme and its host developed huge influence in the Republican Party and the US conservative movement.
President George HW Bush appeared on the programme during his re-election campaign in 1992, while his son George W Bush appeared six times - before, during and after his time in office. President Donald Trump also came on the show in January 2020, when Limbaugh - an ardent advocate of US interventions abroad - praised him for ordering a US drone strike that killed Iranian General Qasem Soleimani.