Last year's finalists Rudar and Budućnost received a bye to the Second Round. The remaining 14 matches were played on 15 September 2010, with the exception of the Kom/Petrovac match, which was postponed until 22 September 2010.
The 14 winners from the First Round and last year's cup finalists, Rudar and Budućnost, compete in this round. Starting with this round, all rounds of the competition will be two-legged except for the final. The first legs were held on October 20, 2010, while the second legs were held on November 3, 2010.