Her version of Snow Patrol's 'Run', which became available to download seven days ago, debuts at number one this week.
It becomes her third chart-topper - following her X Factor winner's song 'A Moment Like This' in 2006 and 'Bleeding Love' last year.
Take That slip to two with 'Greatest Day', while Britney Spears jumps to a new peak of three with 'Womanizer'.
Meanwhile, Katy Perry climbs to a new peak of four with 'Hot N Cold', while Kings of Leon leap from 15 to ten with 'Use Somebody'.
Outside of the top ten, notable gains come from Miley Cyrus, who jumps from 56 to 25 with '7 Things', and Will Young, who advances from 63 to 33 with 'Grace'.
The top ten singles in full (click to read our reviews):
1. (-) Leona Lewis: 'Run'
2. (1) Take That: 'Greatest Day'
3. (6) Britney Spears: 'Womanizer'
4. (5) Katy Perry: 'Hot N Cold'
5. (4) The Killers: 'Human'
6. (2) Beyoncé: 'If I Were A Boy'
7. (3) T.I. ft. Rihanna: 'Live Your Life'
8. (9) Akon: 'Right Now (Na Na Na)'
9. (6) Alesha Dixon: 'The Boy Does Nothing'
10. (15) Kings of Leon: 'Use Somebody'
Source: Official Chart Company
> Click here for this week's UK albums chart