Because it originates from the word mistress
There is no valid reason for the letter 'r' being used as the middle letter of the term 'Mrs.' but when we dig into the full form from which this term has been taken, it might put some focus on the reason. The term 'Mrs.' is an abbreviated form of the word mistress and another term that has been derived from the same word is Miss. But Mrs. is used only for a married woman and Miss is used for an unmarried one, so probably the letter 'r' is used to put emphasis on the term married as the letter 'm' is already in use in the term Mrs.. Though this reason sounds plausible, nobody has come with a concrete evidence in support of the hypothesis that why the letter 'r' is being used as such.