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The Democratic rising star is joining in the race to take on Republican President Donald Trump next year.
Mr O'Rourke, 46, is the 15th Democrat to declare his bid for the White House.
In last year's mid-term election, he ran a tight race against Republican Ted Cruz for his Senate seat, though it proved ultimately unsuccessful.
But he did better than any Democrat in Texas for decades, running a media-friendly campaign that energised the Democratic Party nationwide and drew comparisons with former President Barack Obama.
He joins a growing roster of people vying for the Democratic nomination - including senators Bernie Sanders, Elizabeth Warren, Kamala Harris, Amy Klobuchar and Indiana Mayor Pete Buttigieg to name but a few.
Appearing alongside his wife in his campaign launch video, Mr O'Rourke said this was the "defining moment of truth for this country and every single one of us".
He said the challenges on the economy, democracy and climate change "have never been greater. They will either consume us or they will afford us the greatest opportunity to unleash the genius of the United States of America".
I am running to serve you as the next president. The challenges we face are the greatest in living memory. No one person can meet them on their own. Only this country can do that, and only if we build a movement that includes all of us. Say you're in: https://t.co/EKLdkVET2u pic.twitter.com/lainXyvG2n
— Beto O'Rourke (@BetoORourke) March 14, 2019
Mr Sanders and former Vice-President Joe Biden, who is expected to announce his White House campaign soon, are leading early polls.
But Mr O'Rourke's success with younger voters and knack for viral moments could change that.
And Mr O'Rourke's online network of donors is just behind Mr Sanders' from his 2016 presidential run, according to the Wall Street Journal.
On Thursday, the Texas Democrat will begin his campaign with a three-day trip to Iowa.
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