In 1903, priest Alexander Nemolovsky published an article in the American Orthodox Messenger, proposing the establishment of a monastery and pastoral seminary in Pennsylvania. This idea quickly gained support among other members of the North American mission. A farm was chosen for construction in the northwestern part of the state, near the town of Mayfield, where Ruthenian immigrants were actively settling.

By 1907, the monastery grounds included a brotherhood building with a dining church in honor of Saint Tikhon of Zadonsk and a shelter for 15 orphans. The brotherhood consisted of an abbot, two hieromonks, and seven novices.

One of the first to be buried in the monastery cemetery was Saint Alexius Tovt, who passed away in 1909. Seven years later, his remains were transferred to a special crypt behind the altar wall of the monastery church. In 1941, a chapel was built in the center of the old cemetery site in memory of Metropolitan Platon (Rozhdestvensky), which was replaced with a new one in 1999.

Traditionally, the pilgrimage to Saint Tikhon Monastery takes place on the weekend before or after the American Memorial Day, which is usually observed on the last day of May.