The previous year's winners were De Graafschap, who were replaced by last-placed 2009–10 Eredivisie club RKC Waalwijk.
The league featured 18 teams, two fewer than its previous season, following the exclusion of HFC Haarlem from professional football and the relegation of FC Oss to the 2010–11 Topklasse.
On May 12, 2010 BV Veendam was declared bankrupt due to financial troubles, with FC Oss consequently expected to be readmitted into Eerste Divisie to replace it; however, the verdict was overturned later in June, and the club was thus allowed to play in the season with a reduced budget.
From this season on, the last-placed team would be relegated to the Topklasse, and replaced by the winner of the newly established third tier.
Excelsior and VVV-Venlo joined the Eerste Divisie-teams for the playoffs, after finishing 16th and 17th in the Eredivisie.