Wycombe Wanderers, promoted from League Two last season, host United on Saturday Augst 6 - the opening day of the season.
"They (Scunthorpe) have just come down from the Championship and we've just gone up so it will give us a good indication of how far we've come," said Chairboys boss Gary Waddock, speaking to his club's official website.
"It's a difficult start, but we're up for the challenge. To start at home is great."
The Iron follow that up with a trip to Accrington Stanley in the first round of the Carling Cup, then host Preston North End and Oldham Athletic in the league.
Dennis Booth, Preston's assistant manager, expects a cagey game when the Lilywhites head back to North Lincolnshire.
"We know Scunthorpe pretty well and played really well against them last season, but like most clubs they'll have changes in personnel," he said.
Although the Iron were 3-2 winners at Deepdale, the Lancashire side more than exacted revenge with a 3-0 win in the reverse fixture at Glanford Park.
The dreadful United performance that evening led to Ian Baraclough's reign as manager coming to an abrupt end with a late-night sacking by the club's board of directors.
Paul Dickov's Oldham side will be the Iron's second home opponents of the season, as they complete a quickfire double of Lancashire opponents for the Iron.
"There is no question it is a tough start when you look at the first six games, in which we play some big clubs," he said.
"Apart from Sheffield United and Scunthorpe, who have come down, we have play-off finalists Huddersfield and Rochdale here and difficult away games at Yeovil and Colchester."