The collaboration climbs a single place to reach number one after four weeks inside the top three.
It marks the first number one in the UK for Spears since her 2004 chart-topper 'Everytime', making it her sixth number one single.
Spears said of her number one: "I'm ecstatic that 'Scream & Shout' has been so well-received in the UK. will.i.am is one of my favourite people to collaborate with and I'm just so happy that people really love the song."
will.i.am added: "I am proud and honoured to still have huge success at this stage of my career. I'm so happy I wanna scream and shout."
The track sold 62,000 to reach the top, 13,000 copies ahead of nearest rival Taylor Swift, who rises three places to two with 'I Knew You Were Trouble'.
James Arthur drops two to three with 'Impossible', while Rihanna climbs three to four with 'Stay'. Calvin Harris and Tinie Tempah rise ten spots to five with 'Drinking From the Bottle'.
David Bowie's comeback single 'Where Are We Now?' is a new entry at six, selling 30,000 copies since its surprise release on Tuesday.
The track did not reach the midweek chart on Wednesday due to a sales data issue, in relation to an iTunes deal which allowed fans who pre-ordered Bowie's new album The Next Day to get a free copy of the single.
However, The Official Charts Company were able to differentiate between 'instant grat' downloads and paid downloads in time for the chart announcement. It has also been confirmed that Bowie would not have topped the chart if the free downloads were also included.
'Where Are We Now?' is David Bowie's first UK Top 10 single since 1993's 'Jump They Say', and his 23rd overall.
Elsewhere, Vato Gonzalez and Lethal Bizzle enter at 20 with 'Not a Saint', while Kanye West and Jay-Z re-enter at 22 with 'Clique'.
Emeli Sandé re-enters at 23 with 'Clown', with Jake Bugg debuting at 26 with 'Lightning Bolt'. David Guetta's latest release 'Just One Last Time' is new at 27.
BBC Sound of 2013 winners Haim score a new entry at 32 with 'Don't Save Me'. Bon Jovi land at 38 with new single 'Because We Can', followed by Matrix + Futurebound's 'Magnetic Eyes' at 39.
Jameela Jamil presented the BBC Radio 1 chart show for the first time today (January 13), becoming the first full-time female presenter of the long-running programme.
Watch the video for 'Scream & Shout' below:
Source: Official Charts Company
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