Leona's first US single Bleeding Love hit the number one spot over 20 years after British pop star Kim Wilde last topped the charts with her 1987 version of The Supremes hit You Keep Me Hangin' On.
Industry sources say her appearances on chat-shows Oprah and Jay Leno prompted a surge in download sales, while the Hot 100 chart also counts radio airplay.
Chart topper: Leona Lewis, seen here on chatshow Jay Leno on Monday, is poised to become the first British female to top the US charts for 20 years
Endorsement: Leona, seen here with mentor Simon Cowell and Oprah Winfrey, received a ringing endorsement from the billionaire chatshow host last week, who described her as 'the real deal'
Despite stiff competition from well-established artists such as Madonna, and R&B superstar Usher, newcomer Leona, 22, is set to eclipse the success of musical contemporary, Amy Winehouse, whose album Back to Black debuted at No.7 in the US charts.
Winehouse has sold 1.5 million copies of her Back To Black album in the US, but has not topped the singles chart despite her Grammy awards.
Leona earned a ringing endorsement by Oprah Winfrey on nationwide television last week, when she appeared on the show with mentor Simon Cowell.
After earning a standing ovation with her performance, Oprah told the Hackney born singer, and former receptionist: "You're the real-deal girl. Talk about a star is born."
During the show, Simon paid off a family's £80,000 mortgage after being touched by the plight of their three-year-old daughter, who has a rare form of cancer.
After Leona won the X Factor, in a bold move, Cowell took her to the US and negotiated a £5 million album contract with Clive Davis, the music mogul who signed Whitney Houston.
She was sent to record with top US producers and a slick video, designed for MTV, was filmed for Bleeding Love. It later became the biggest-selling British single last year.
Stunning: Leona's single Bleeding Love was the UK's biggest selling single last year. She has auctioned the Roberto Cavalli dress she wore at The Brits last month, it raised £3,200 for charity
Despite her runaway success, last month Leona was snubbed at the Brits, and failed to win any of the four awards she was nominated for.
But the big-hearted star shrugged off her disappointment, and has auctioned off her Brit Awards dress raising £3,200 at auction for Sport Relief.
The stunning purple gown was specially designed for her by Roberto Cavalli.
Cavalli said: "It has been a great pleasure for me to work with Leona right from the start. She has beautiful eyes, an incredible voice and a fresh and positive attitude.
"Her stellar, instant success is the proof that real talent still counts. Leona is becoming a role model - her fame is all about strong will and hard work."
Meanwhile, a spokesperson has denied reports that Leona is considering undergoing throat surgery to end recurring bouts of tonsillitis.
He said: "She has got a pretty bad throat. She just can't shake it off at the moment but I don't think she needs to have an op."
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