The 2005–06 season was the 103rd in the history of the Southern League, which is an English football competition featuring semi-professional and amateur clubs from the South West, South Central and Midlands of England and South Wales.
At the end of the season Eastern and Western divisions were restructured after a single Division One of the Isthmian League was divided into Division One North and Division One South, while large number of the clubs left to the Isthmian League. For the next season regional divisions were renamed Division One Midlands and Division One South & West.
The Premier Division consisted of 22 clubs, including 16 clubs from last season, and six new clubs:
Salisbury City won the division and were promoted to the Conference along with play-off winners Bedford Town, both clubs for the first time in their history. Aylesbury United, Chesham United and Evesham United were relegated to the Division One.
The Eastern Division consisted of 22 clubs, including 15 clubs from last season, and seven new clubs:
Boreham Wood won the division and returned to the Premier Division of the Isthmian League after relegation in 2003. Runners-up Corby Town and play-off winners Stamford promoted to the Premier Division. At the end of the season a single Division One of the Isthmian League was divided into Division One North and Division One South. Fifteen Eastern division clubs left the Southern League and joined new divisions, while Eastern and Western divisions were renamed Division One Midlands and Division One South & West.
* after extra time
The Western Division consisted of 22 clubs, including 15 clubs from last season, and seven new clubs:
Clevedon Town won the title and were promoted to the Premier Division along with play-off winners Hemel Hempstead Town, returning after relegation in 2004. Runners-up Ashford Town were promoted and transferred to the Isthmian League Premier Division. Thame United finished bottom and were the only Southern League club relegated from the league. Remaining clubs were divided between the newly formed Division One Midlands and Division One South & West.