The rapid growth of the north side of Spokane, Washington caught the attention of the Reverend Thomas Watson, pastor of First Presbyterian Church. He and Howard Stratton decided to do something about it. Watson, Stratton and a few others met together on January 27, 1888 and again on February 3, 1888. At the latter meeting Centenary Church was organized. It was incorporated on March 23, 1888 with nineteen members. Its first pastor was the Reverend Herbert G. Dennison. Of special interest was the founding in Centenary Church of "Father's Day" at the suggestion of Sonora Smart Dodd. The first observance was held on June 10, 1910 and it has been celebrated nationwide ever since.

The Centenary Church at Sinto Avenue and Wall Street was partially destroyed by fire on March 2, 1917. Ground was broken May 17th for a new edifice at Knox Avenue and Post Street with the name changed to Knox Presbyterian Church in honor of John Knox, the founder of Presbyterianism. The first service was held in the new building on November 11, 1917, less than six months from the time of groundbreaking. On December 1, 1918 the Reverend W. S. Middlemass of Red Wing, Minnesota was called at a salary of $1800 and free use of the manse. At the end of 1918 church membership was 338 and the outstanding indebtedness was $12,000. After Mr. Middlemass left, the Reverend Charles F. Koehler served from 1923 until 1946. His ministry was notable for 34 young people who went into various forms of full-time service for Christ. On February 17, 1957 a remodeled church was dedicated. The structure included new east and west entrances , extensive alterations to the sanctuary and educational units, and electrical and heating improvements.

The Reverend Leigh P. Taylor began the second longest pastorate at Knox Church on August 1, 1967. His coming inaugurated one change in the relationship between church and pastor. He was offered the choice of the use of the manse or a manse allowance. He accepted the allowance and served the church for 23 years. He became very involved in the establishment and progress of "Operation Nightwalk" which began in October 1970. Spokane ministers took turns walking the streets of downtown Spokane at night to be available to individuals with problems of homelessness and despair. In 1980 the Reverend Joel Crosby began his ministry at Knox. His tenure included the formation of a "Trainee" ministry to conduct an active ministry with children, youth and adults during summer times. The program was supplemented by an "Enabler" ministry in which employed young people were encouraged to give spare time to church service. The history of Knox Church would not be complete without mention of the unique ministry of Albert Arend. He was born June 5, 1900 and joined Knox Church in 1910. At age 22 he became an elder of Knox Church. During the years that followed he spearheaded the Christian Endeavor movement at the church. Of special interest also is the correspondence relating to the rescue of the Reverend Leon I. Rosenberg from Nazi persecution in Lodz, Poland just before WWII.