The 2010–11 Southampton F.C. season was the club's 71st and sixth consecutive season in The Football League, and their second in League One. Having narrowly missed out on the chance of promotion the previous season, Southampton were again seeking to reclaim their place in The Championship by being promoted in 2011. Before the commencement of the campaign, Southampton were slated as the favourites to win the League One title by a number of bookmakers, commentators and fans.

This season marked the 125th anniversary of the club's formation in November 1885, which was celebrated in a number of ways. Firstly, the four-year sponsorship deal with Flybe ended, with shirts for the anniversary campaign designed without a sponsor; secondly, the new shirts feature a redesigned club crest recognising the 125 years of the club's life; and thirdly, a new home shirt was designed to be reminiscent of the first ever worn by players of the club, being white with a red sash. The club also released a new black away kit, also without a sponsor, designed to be similar to the popular away kit worn in the 2006–07 season.

On 11 August 2010, the season was marked by early tragedy after the death of club owner Markus Liebherr, who had brought Southampton out of administration in July 2009. As a result, the following weekend's match against Milton Keynes Dons was postponed, and there were discussions of plans for a major club tribute to Liebherr. The club also faced major change later in the month, as manager Alan Pardew was sacked shortly after a 4–0 win against Bristol Rovers, a decision which the club deemed "essential" to "achieve its well known targets". On 12 September, after much speculation, the appointment of replacement manager Nigel Adkins was confirmed.

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