O'Rourke paused his campaign for almost two weeks, then returned as a strident advocate for gun control measures - including mandatory buybacks of assault-style rifles. When he returned to the campaign trail, he reoriented his focus on gun control.
He called the bloodshed a "consequence" of Mr Trump's anti-immigrant rhetoric.
Shortly after his exit from the race, Trump took aim at O'Rourke on Twitter.
His position led to criticism from Democrats in Washington, including Senate Minority Leader Chuck Schumer.
Some presidential hopefuls can run unsuccessful campaigns and end up with an elevated stature among party faithful - with more political prospects than when they began.
In his farewell message, O'Rourke said he would support the Democratic nominee. Trump wrote, in a reference to a quote in the Vanity Fair article. He later described the cover, along with his choice of words, as a mistake. But his fund-raising cratered nearly immediately. And he raised $6 million on the first day of his campaign.
O'Rourke, who represented El Paso in Congress, entered the race as one of the most talked-about candidates following his narrow loss to Sen.
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How did Mr O'Rourke quit?Mr O'Rourke, whose campaign started high and trended only downward, was not so fortunate.
To Mr. O'Rourke and his allies, it has been evident for some time that he was confronting a vanishingly slim path forward. Mr. O'Rourke told them he was not running for Senate, according to people familiar with the matter.
Mr O'Rourke was expected to address crowds later on Friday at an event in Iowa. I know that you did it not for me personally, not for the Democratic Party, but for our country at this defining moment.
The latest New York Times-Siena College poll released on Friday showed that Warren is now leading in Iowa, an early voting state, and is holding a slim lead over Sanders.
O'Rourke was not likely to make this month's debate stage or qualify for future debates. Speaking at a rally in Tupelo, Mississippi, the president branded O'Rourke a "poor, pathetic guy".
When O'Rourke first announced his presidential candidacy in late March, he dominated headlines and hit his polling peak.
"Hell, yes, we're going to take your AR-15, your AK-47", he firmly declared during the third Democratic debate, which took place just a month earlier.