Huth, who had been expected to move on this summer with interest from his German homeland, has been selected alongside David Wheater at the heart of the defence.
And Southgate has sprung a couple of other surprises, with highly-rated defender Rhys Williams asked to play in the middle of midfield at the expense of the more experienced Julio Arca.
New signing Leroy Lita has been included on the bench, with Jeremie Aliadiere deemed fit enough to partner Marvin Emnes in attack after illness.
Southgate's other two summer signings, goalkeeper Danny Coyne and winger Mark Yeates, also start against the Blades.
MIDDLESBROUGH (4-4-2): Coyne; McMahon, Wheater, Huth, Grounds; Yeates, Digard, Williams, Johnson; Emnes, Aliadiere. Subs: Steele, Hoyte, Taylor, Lita, ONeil, Arca, Franks.
SHEFFIELD UNITED (4-3-2-1): Bunn; Taylor, Kilgallon, Morgan, Walker; Dunn, Monygomery, Howard; Treacy, France; Henderson. Subs: Bennett, Evans, Reid, Cotgterill, Bromby, Sharp, Little.
For reaction and report of tonight's Championship opener see tomorrow's The Northern Echo.