The Sanctuary is the heart of the Abbey, where the High Altar stands. The altar and reredos above it were designed by Sir George Gilbert Scott in 1867. The Last Supper mosaic is by Antonio Salviati. On the altar are two candlesticks bought with money bequeathed by a serving maid called Sarah Hughes in the 17th century. The inscription along the top reads "The kingdoms of this world are become the kingdoms of our Lord and of his Christ" (from the book of Revelation). There are four large statues of Moses, St Peter, St Paul and King David flanking the altar and the doors leading into St Edward's chapel, which is immediately behind the screen. Also in this area is the Abbey Lectern, given in memory of the missionary William Carey.

In front of the High Altar is another of the Abbey's treasures - a marble pavement dating from 1268. The method of its decoration is known as Cosmati work, after the Italian family who developed the technique of inlaying intricate designs, made up of small pieces of coloured marble, into a plain marble ground. Materials used include onyx, porphyry, serpentine and coloured glass. It is 24 feet 10 inches square and there were three Latin inscriptions incorporated in it. One calculated that the world would last for 19,683 years. The pavement is currently undergoing restoration.