Valletta were the defending champions, but lost in the Final to Floriana.
Calendar
Matches will begin on 10 November 2010 and conclude with the final on 22 May 2011.[1] For the second straight year, four teams will receive a bye directly into the quarterfinals.
Entering this round was the winner from the preliminary round along with the six Maltese Premier League clubs which finished last season between 5th and 10th place in the league, the remaining eight clubs from the First Division and the reigning Gozo First Division champions. These matches took place from 12 to 14 November 2010.
Valletta and Floriana have met together in Maltese FA Trophy final six times before, having previously met in 1957, 1960, 1976, 1977, 1978, and 1994. When meeting in the finals, Valletta won three times (1960, 1977 and 1978). Floriana won three Times (1957, 1976, and 1994).
The last time Floriana and Valletta met together in the FA Trophy was the 2008–09 Quater-finals when Valletta beat Floriana by 4–1 on penalties when the match ends 2–2 draw.