Belgium's capital city was due to have three group fixtures and one last-16 tie, but delays over a new stadium forced UEFA's executive committee to make changes to the schedule.
The announcement means London will now host seven games in total, with Wembley already confirmed for the semi-finals and final.
Despite being in the running as alternative options, Cardiff's Principality Stadium and Stockholm's Friends Arena missed out on the chance to replace Brussels.
While the full schedule is still to be confirmed by UEFA, the Stadio Olimpico in Rome will stage the opening game.
Each host nation that qualifies will be guaranteed two home matches in the group stage.