For much of their early existence Worksop Town played in the Midland League. Two notable FA Cup runs occurred during this period. In the 1907-08 season, the club reached the First Round Proper (the equivalent of the modern day competition's Third Round), and were drawn away against Chelsea. Although losing 9-1, the game drew an attendance of 70,184, a club record which still stands today. Another cup run occurred during the 1920-21 season, with Worksop becoming one of the famous FA Cup minnows by holding Tottenham Hotspur to a 0-0 draw at the Division One side’s White Hart Lane ground. The replay was controversially held at White Hart Lane for financial reasons, and saw Worksop lose 9-0. Supporters who had expected the replay to take place at Central Avenue showed their disappointment by staying away from subsequent home matches, an action that for a time saw the club’s debts mount.
In the mid 1960s Worksop won the Midland League and became founder members of the Northern Premier League. After one season the club were relegated back to the Midland League. By the late 1970s they had gained re-entry into the Northern Premier League. Around this time, Worksop had another relatively successful FA Cup run, reaching the First Round during the 1978-79 season, losing 5-1 away to Barnsley.
For the start of the 2004-05 season, Worksop became founder members of the Conference North, created as part of Phase One of the restructuring of non-league English football. The latter half of that season saw the club hit financial difficulties; as a result, they were deducted 10 points, transforming the team's season from a credible promotion challenge to a relegation battle. The club eventually finished 17th in their first season of Conference North football. The 2005-06 season saw the team further struggle, finishing 19th in the division, despite an impressive FA Trophy run which saw them beat Conference National sides Burton Albion and Accrington Stanley. 21st place in 2006-07 signalled relegation for Worksop, and with it a return back to the Northern Premier League Premier Division.