Promoted from the Conference as champions at the end of last season, Luton kicked off the 2014-15 campaign with a 1-0 win at Carlisle United, while Cambridge triumphed by the same scoreline at home to Plymouth Argyle.
Luton, who play host to AFC Wimbledon on Saturday, are one of the favourites to win promotion to League One this term, but manager John Still has urged caution.
Speaking after Saturday's victory, Still told the club's official website: "It is important for everyone inside the club to remember that what we are doing at the moment is making steps, small steps.
"You know I will not get too excited until the job is done and we have a lot of work to do to get to where we want to be.
"As the old saying goes, we will always just take one step at a time."
Cambridge's league campaign steps up a notch as they visit Fratton Park to face Portsmouth - another of those clubs tipped to make it out of the division this season.
Morecambe were the big winners on the first day of the League Two season, winning 3-0 at Dagenham and Redbridge, and will fancy their chances of claiming another win against a Newport County side who opened with a 2-0 home defeat to Wycombe Wanderers.
Many had tipped Wycombe for relegation this season, but they will be eager to continue proving their doubters wrong when they host Carlisle.
Down in the south-west Plymouth host Exeter City in the first local derby of the new season.
Cheltenham Town and Burton Albion won on the road on Saturday, but must now deliver on home soil against Accrington Stanley and Dagenham respectively in order to maintain their 100 per cent records.
Tranmere Rovers, who were taken over by former Football Association chief executive Mark Palios and his wife Nicola earlier this week, face a trip to Shrewsbury Town, who could hand a league debut to former Tranmere man Andy Robinson.
In the weekend's remaining fixtures, Hartlepool United host Bury, Oxford United are at Mansfield Town, Stevenage travel to Southend United and York City face Northampton Town.
