Southampton start their Coca-Cola League One season on minus 10 points and host last season's beaten play-off finalists Millwall.
The Saints meet the Lions, who lost 3-2 to Scunthorpe at Wembley in the play-off final in May, on August 8 having been punished by the Football League in April after their holding company entered administration.
Southampton, who meet Exeter on Boxing Day and Southend on the final day of the season on May 8, were joined in the drop from the Coca-Cola Championship by two other ex-Premier League sides in Norwich and Charlton.
Norwich face East Anglia rivals Colchester in their opening game at Carrow Road, while the Addicks host Wycombe.
The Wanderers were promoted to the Football League's third tier on the final day of the season, joining Brentford and Exeter in ascending up the league.
Brentford, who lifted the League Two title last term, face the long trip to Carlisle on the opening day, while Exeter visit Leeds.
Leeds stumbled in their bid to return to the Championship once again last term and will begin the League One season as one of the favourites.
Simon Grayson's side meet Charlton on October 3 and in a potentially decisive clash at The Valley on May 1 - the penultimate day of the season - and Norwich on October 17 and March 27.
MK Dons, who lost to Scunthorpe in the play-off semi-final, meet Hartlepool on the opening day, and face Charlton, Norwich, Wycombe and Leeds in a testing April schedule.
Gillingham, who won last month's League Two play-off final at Wembley, travel west to Swindon on the opening day.
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