About twenty years before the events of the novel, he lived in Westmoreland. Dr Haydock had a practice near there, and they got to know each other.
Colonel Protheroe's first wife left him some time before he moved to St. Mary Mead. Five years before the events of the novel, he married his second wife, Anne. His daughter from his first marriage, Lettice Protheroe, lived with them at Old Hall.
Colonel Protheroe was described as having a "stentorian voice", as he tended to raise his voice because he was slightly deaf. He was also described as "the kind of man who enjoys making a fuss on every conceivable occasion". This led him to go over the Church accounts, after Mrs Price-Ridley complained to him about the missing pound note, which she had put into the offertory bag. He had also had disputes with Dr Stone, and had turned Lawrence Redding out of Old Hall, because he was painting Lettice in her bathing dress.
On the evening beforenhis death, Colonel Protheroe received a visit from Mrs Lestrange. Parts of their conversation were overheard by Gladys, a kitchen maid. The interview was not a peaceful one, with Mrs Lestrange wanting him to do something, and him refusing. It is later revealed that Mrs Lestrange was actually the first Mrs Protheroe, and the mother of Lettice. She had gone to see Colonel Protheroe to tell him that she was dying, and that she wished to see Lettice.
On the day of the murder, Colonel Protheroe went to the vicarage to go over the Church accounts with Reverend Clement. However, when Reverend Clement entered the study, he found Colonel Protheroe dead from a shot to the head. A note from Protheroe to Reverend Clement was found, saying that he could not wait any longer. It is later revealed that this note was not written by Colonel Protheroe, but was planted by the murderer. The real note that Colonel Protheroe had written was found later, and it concerned the person responsible for taking from the church funds.