The Scottish DJ has teamed up with Ne-Yo for 'Let's Go', which is currently out in front on the UK midweek chart update.
Carly Rae Jepsen has slipped to two with 'Call Me Maybe', fun. remain at three with 'We Are Young' and Conor Maynard falls to four with 'Can't Say No'.
Jessie J and David Guetta remain firm at number five with 'LaserLight', while John Legend's 'Ordinary People' slips six places to 10.
The Voice UK continues to affect the singles chart following performances of popular songs on the show.
Stereophonics' 'Dakota' zooms up to 18, U2's 'With Or Without You' is at 35, Kings of Leon's 'Sex On Fire' is at 37 and Madcon's 'Beggin'' is at 38.
Over on the album chart Jack White is set to claim the number one position with his debut solo album Blunderbuss.
Rufus Wainwright follows at two with Out Of The Game, Adele's 21 falls to three and Lana Del Rey is at four with Born To Die.
> View the current singles top 100 here
Listen to Calvin Harris and Ne-Yo's 'Let's Go' below: