Meredith holds the title of Knight Commander in Kirkwall at the start of the events of Dragon Age II. In Act 1 Meredith initially denies all Fereldens from entering Kirkwall, including Hawke and his/her companions, she also makes a brief appearance right before you begin your first conversation with Bartrand. She keeps strict watch on the mages of the Circle, and champions the use of harsh measures to prevent apostate mages, though she denies Ser Otto Alrik the use of his "Tranquil Solution" plan to turn all mages in Kirkwall into Tranquils. She is also the real political power in Kirkwall, as the current viscount fears to go against her wishes. Meredith's obsession with controlling mages borders on paranoia, and she is willing to oppress, intimidate, and neutralize anyone to root out corruption with in the mages. She appears to view the very existence of magic and mages as a threat to the general populace.

During the Qunari invasion of Kirkwall, Meredith saved Hawke and his/her companions from a saarebas. Soon after Meredith joined forces with both Hawke and First Enchanter Orsino in an attempt to regain the Viscount's Keep. When Hawke is able to convince the Qunari to leave or defeats their Arishok in combat, Meredith appoints Hawke Champion of Kirkwall. She does so reluctantly, however, as she viewed Hawke's new influence in the city as a potential threat and initially viewed the foreign Hawke with disdain.

At some point after Hawke accompanied Bartrand and Varric into the Deep Roads, Meredith was able to obtain most of the lyrium idol which they had discovered. She had this shaped into a sword for herself. However, the unknown type of lyrium it was composed of caused her to go insane, just as it had done to Bartrand. This development exacerbated her paranoia and prejudices against mages, and tensions between herself and First Enchanter Orsino rose over the three years following the death of Viscount Marlowe Dumar. She had Kirkwall placed under martial law and refused every attempt to replace Dumar. According to Ser Karras she went as far as to request the Divine in Val Royeaux for the Right of Annulment even prior to the beginning of Act 3.

After Anders destroyed the Chantry in his attempt to free the mages (The Last Straw), Meredith retaliates by invoking the Right of Annulment on the Circle, even though they were uninvolved (as Anders was an apostate mage). The Champion can choose to side with her or support the Circle. Regardless of whether Hawke sides with the Circle or Templars, Meredith will turn on Hawke, accusing the Champion of conspiring the whole ordeal and orders the Champion to be executed. Her second-in-command Cullen, who was usually supportive of her harsh measures, sees her insanity has become so pronounced and orders her to step down.

This serves to increase her paranoia, as she accused all of her subordinates of being blood mage thralls. She then reveals the sword made of the lyrium idol found during Champion's earlier trip to Deep Roads. The sword grants her superhuman abilities and the capability of animating statues; nevertheless, the Champion and their companions are able to defeat her. In the midst of the battle, Meredith begins to question if what she was doing was right but her doubts are quickly washed away. As she refused to admit defeat, her sword then shatters and Meredith withers and is petrified in lyrium. Lightly implied, it seemed that the sword made of the lyrium idol corrupted and drove her insane, just like what happened to Bartrand.