Murphysboro's Lodge was chartered on October 3, 1866. In its inaugural year, Murphysboro Lodge No. 498 was part of District No. 1; this included the counties of Alexander, Jackson, Johnson, Massac, Monroe, Perry, Pulaski, Randolph, Union, and Washington. The Lodge first held its meetings in the Jackson County Courthouse. There were twenty members that met on the "Monday on or before full moon."

Serving as its first Worshipful Master was John Ford, also Murphysboro's first mayor. He would later be appointed as High Priest of the Royal Arch Chapter when it was established in 1875. The York Rite would continue to prosper and the temple was joined by an active chapter of the Order of the Eastern Star. As was typical of the early days of Freemasonry, many of the Lodge's Past Masters were prominent citizens of Murphysboro. More specifically, they were heavily involved with the local schools and educational institutions.

In 1870, it was said that "The lodge at Murphysboro is well officiated, has a good hall, and is in a harmonious and prosperous condition" when the Grand Lodge came down to lay a local cornerstone. The Lodge later moved to the second floor of Dr. Bierer's Store and then over the store of Kennedy & Ross. The latter was opposite of the Logan House Hotel.

A new building was built in 1920 and dedicated the next year. Its construction was almost entirely concrete and built to the style of a miniature Art Deco palace. Its architect was the renowned Rudolph Zerses Gill, a member of the Lodge. The halls of Hurst and Herrin's Prairie were built near-identically, but at a much smaller scale.

This location was one of the few surviving buildings in the wake of the Tristate Tornado of March 18, 1925. The upper level was used as a temporary hospital for minor injuries, while it is said the lower part served as a morgue. The lodge hall was -and still is- described as "one of the best temples" in southern Illinois.

La Fayette Lodge No. 657, of Grand Tower, merged with Murphysboro in 1985. More recently, the Lodge absorbed Carbondale's Shekinah Lodge No. 241, in 2020. The next year saw the dissolution of the local Order of the White Shrine due to its members aging out. However, groundwork for a new Bethel for Job's Daughters was started soon after and is expected to be chartered by the end of 2022.