Simon Neil and the lads will play Bellahouston Park on Saturday August 27.
The news comes just days before the lads reveal their new single on Radio 1 this Monday.
They recently spent time in Los Angeles recording their seventh studio album, and their Glasgow Summer Sessions will see them perform here for the first time since their three consecutive night run at Glasgow Barrowland in 2014, which saw the band play two albums per night.
Biffy said: "We are delighted to be playing our biggest ever headline show in Glasgow in August. We're gonna bring all the Bellahoustons and whistles and give us all a night we'll never forget."
Over 35,000 fans are expected to welcome the home-grown heroes back to the city festival with a full supporting bill – headed up by Fall Out Boy – to be announced over the coming months.
An adrenaline-charged set is on offer similar to Biffy Clyro’s headline performance at T in the Park 2014.
As well as chants of Mon The Biff fans can expect classics like Many of Horror, That Golden Rule, Mountains and new material from their upcoming seventh album.
Tickets will go on general sale at 9am Wednesday March 23 via www.glasgowsummersessions.com or by calling 08444 999 990
Travel and event information is available at www.glasgowsummersessions.com and by following @GSSFestival on Twitter.
