Mitt Romney will pledge to "restore the promise of America" in a much-awaited speech to the Republican convention in Tampa, Florida.
Mr Romney is also expected to discuss his Mormon faith and business record as he accepts his party's presidential nomination in the prime-time address.
US media report that actor Clint Eastwood will appear as a "mystery guest" speaker during the evening.
Mr Romney faces President Barack Obama in a tight race for the White House.
According to excerpts of the speech released by his campaign, Mr Romney is expected to say: "Many Americans have given up on this president but they haven't ever thought about giving up.
"Not on themselves. Not on each other. And not on America.
"I wish President Obama had succeeded because I want America to succeed," Mr Romney will say.
"But his promises gave way to disappointment and division. This isn't something we have to accept."
Florida Senator Marco Rubio and Mr Romney's former rival presidential candidate, Newt Gingrich, are due to speak earlier on Thursday evening.
Mr Romney is also expected to lay out his vision for US economic recovery - a subject his running mate, Paul Ryan, touched upon in his address on Wednesday - and to dwell on his stellar business career.
On the campaign trail, Democrats have attacked Mr Romney's record at private equity firm Bain Capital and raised questions about why the candidate has refused to release more than two years of tax returns.
Earlier on Thursday, the Romney campaign released a video hitting back at criticism about his time at Bain Capital.
Mr Romney may also talk about his Mormon faith - a central commitment in his life - which has been viewed with caution by some evangelical Christian voters.
A video about his life is due to play just before he takes to the stage.
He is expected to be introduced by former athletes - Mr Romney ran the 2002 Salt Lake City Olympic Games - and members of the Mormon church.
Mr Romney's former business associates - such as former Bain Capital colleague Bob White and Tom Stemberg, the president of stationery giant Staples - will also praise the candidate.
Thursday evening's festivities are expected to culminate with the entire Romney family - his wife, five sons and their wives and 15 of his 18 grandchildren - on stage with him as thousands of balloons are released over the convention floor.
Analysts say Mr Romney must use this speech to connect with voters. Low favourability ratings have dogged the former Massachusetts governor throughout his campaign and he trails Mr Obama in likeability.
In an email to donors on Thursday, Mr Romney said: "I commit to you that I will be the president this moment demands."
Mr Romney's speech will cap three days of pageantry at the Republican convention, which started a day late because of Tropical Storm Isaac.
This is Mr Romney's second run for the White House, after an unsuccessful bid in 2008.
On Wednesday, his running mate spoke of his family and childhood while also pledging a "turnaround" for America.
But fact-checkers said there were a number of inaccuracies in Wisconsin congressman Ryan's speech.
Mr Romney's wife, Ann, addressed the convention on Tuesday, making an appeal to female voters, a demographic with which the Republican candidate has had trouble connecting.