Luton's five-year spell in non-league came to an end when they lifted the Conference title last season, finishing 19 points clear of Cambridge, who followed them up via the play-offs.
Cambridge had rivalled Luton for much of the campaign before falling away early in the year, but Plymouth's visit to the Abbey Stadium represents the end of a nine-year Football League exile for the hosts.
And Richard Money is quietly confident of his side's chances against Plymouth and beyond.
"You only have to read a few of the comments in the national press to understand that they have absolutely no idea of what we've got in our team," he told BBC Radio Cambridgeshire.
"We're going into the unknown a little bit. I know this league and have been fortunate enough to take [Walsall] to the championship in this league.
"I have a fair idea of what it's about. But to the players and the fans it may be a bit unknown.
"But we're a little unknown to a lot of people."
In contrast to Cambridge and Luton's upward momentum, Tranmere Rovers, Shrewsbury Town and Stevenage will all be keen to halt their slides down the pyramid after relegation.
Rob Edwards' first league game as Tranmere boss sees the visit of last season's play-off semi-finalists York City, while Shrewsbury travel to AFC Wimbledon and Stevenage host Hartlepool United.
Southend United and Burton Albion also extended their season with a play-off appearance last time out and both are on the road at the start of the 2014-15 campaign - taking on Accrington Stanley and Oxford United respectively.
Wycombe Wanderers came perilously close to going down last term, surviving on goal difference, and will hope to start afresh at Newport County, while Chris Wilder begins a season for the first time as Northampton Town boss with a match against Mansfield Town.
Wilder was appointed midway through the 2013-14 campaign and saved their Football League status with a final-day win over former employers Oxford.
Elsewhere, Portsmouth make the relatively short trip to Exeter City, Dagenham and Redbridge welcome Morecambe, while Cheltenham Town travel north to Bury.
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