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.
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.
* 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.