Mr. and Mrs. Shailaja Krishna Murthy is an Romance based movie. In which, Krishna Murthy (Sivaji) is an atheist who travels to Annavaram on the severe insistence of his aunt (Rama Prabha). Sailaja (Laila) is an extremely religious girl who wants to go to USA for further studies. She is also traveling to Annavaram to get blessings of Lord Satyanarayana. Krishna Murthy and Sailaja happen to share the same Berth in the train. When they arrive at Annavaram, they are forced to share the same room as husband and wife (Mr. & Mrs Sailaja Krishna Murthy) due to the local room-allotment rules.
Due to certain incident, Sailaja and Krishna Murthy are separated in Annavaram. Each one of them do not know whereabouts of other person. Sailaja and Krishna Murthy realize that they had fallen in love. They start searching for each other in Hyderabad city. The rest of the story is all about how they find each other.