League One Preview: Sheffield United set for Bristol City test, Barnsley host Crawley
A poor opening to the 2013-14 campaign saw predecessor David Weir lose his job in October after taking just one win from 13 matches.
United subsequently turned to Clough as the man to lead the club out of the third tier of English football and a strong end to the term saw them narrowly miss out on the play-offs in seventh.
Clough also guided the side to the FA Cup semi-finals, with a 5-3 defeat to Hull City at Wembley ending their dreams, and that promising form has raised the already high expectation levels at a club who were in the Premier League just seven years ago.
Saturday's curtain-raiser sees United face another team who have been placed among the favourites for promotion, as Steve Cotterill's City outfit head north looking to put the disappointment of last season - when they finished 12th - firmly behind them.
The encounter promises to be a gripping contest, but Clough will not place too much stock in the result.
"It would be lovely to get off to a great start and be in the top few, but if we're not it's not the end of the world," he said.
"You're talking about a whole new team coming in. Some will settle quicker than others. If things don't go too brilliantly in the first three games we're not going to get too down about it because we'll have 43 to go."
United are joined in League One this season by South Yorkshire rivals Barnsley and Doncaster Rovers, who were both relegated from the Championship last season.
Danny Wilson has had a tough pre-season at Oakwell with Barnsley, as the likes of Luke Steele and Chris O'Grady have departed for pastures new.
However, Wilson is an experienced manager at League One level and will look to make a strong statement at home to Crawley Town.
Doncaster - who were subject to a failed takeover bid from former chairman John Ryan and One Direction star Louis Tomlinson in the close-season - start at Yeovil Town, who are also looking to bounce straight back to the Championship.
Leyton Orient are aiming to recover from May's play-off final defeat to Rotherham United, but face a tricky task on the opening day against a Chesterfield side buoyed by winning the League Two title last season.
Rochdale and Scunthorpe United both achieved automatic promotion to League One last term, with the former hosting last season's play-off semi-finalists Peterborough United, while the latter visit Swindon Town.
Fleetwood Town - who triumphed in the League Two play-off final - welcome Crewe Alexandra to Highbury.
Preston North End finished in the play-off positions in the 2013-14 campaign and start their attempt to reach the Championship at home to Notts County, while MK Dons welcome Gillingham.
Other matches see Bradford City take on Coventry City, Colchester United host Oldham Athletic and Walsall travel to Port Vale.