In January 1901 a Waynesburg Chamber of Commerce was organized with A.I. Cooke as President. This organization, with Cooke still serving as President, was referred to in 1902 as the Waynesburg Board of Trade.  

In 1905 the Waynesburg Merchant’s Association was organized with meetings held every week in the Americus Room of the Greene House on High Street.  This organization was in addition to the Chamber of Commerce.

On December 19, 1916 the Waynesburg Board of Trade and the Federation of Women’s Clubs helped place a Christmas tree in front of the courthouse in Waynesburg for the first time.

The Waynesburg Chamber of Commerce was formed in May 1922 replacing the Board of Trade, with 220 members representing all of the business, commercial and industrial interests of the community. One of the first activities was to sponsor a “Dollar Day” in August 1922, involving thirty-three merchants. This was followed by a style show that attracted some 5,000 people. Another project of the Chamber began in August 1925 was the sponsorship of a Curb Market on Church Street where farmers could sell produce directly to the public. The Chamber, through the 1920’s and 1930’s promoted the building of a standard-gauge railroad to Waynesburg, pushed for the completion of paved highways throughout the county, promoted the organization of volunteer fire company in Waynesburg, urged the establishment of a commercial airport in the county and attempted to attract new industries as well as was in the forefront of all campaigns for community betterment.

The Waynesburg Chamber of Commerce was disbanded in November 1938 and was immediately replaced by the Waynesburg Business Association in December 1938. The Waynesburg Business Association sponsored the first Christmas parade in Waynesburg on Saturday, December 3, 1938 with an estimated 7,000 people in attendance. Santa made news across the state because his truck ran out of gas which delayed his arrival in front of the courthouse.

In 1945, a reorganized Waynesburg Chamber of Commerce was formed.  The Chamber sponsored the first Miss Rain Day contest on the courthouse steps beginning in 1964 with the crowning of the Carla Gray.  The contest continued intermittently until 1979 when the Chamber launched the Miss Rain Day Scholarship Pageant, with the crowning of Lisa Elek. The Chamber then founded Rain Day Scholarship Inc. in 2004 to oversee the Miss Rain Day Scholarship Pageant which continues to this day.

The Chamber also founded Waynesburg Prosperous and Beautiful which began as the Downtown Revitalization Committee to develop a plan to strengthen the economic and historic aspects of the downtown area in conjunction with the National Main Street USA Program.  The funding to start this endeavor was presented to the Chamber by the Downtown Merchants Association when they disbanded in the late 1980’s.

The Chamber assisted in the creation of a county-wide tax abatement program for commercial and residential construction.

In 1996 the Chamber held “A Day of Celebration” in honor of the country’s Bicentennial Year. In 2002 the Chamber contributed towards the renovation of the original Log County Courthouse.

In 2003 the Chamber received the Pennsylvania Chamber of Commerce Executives Certificate for “Approved Chamber Status”, making the Greene County Chamber one of twelve out of one hundred and eighty five chambers in the state to achieve this. 

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The Chamber has annually awarded an educational scholarship of $1500 presented to a Greene County Student meeting certain criteria for consideration since 1990. In 2018 the Chamber began awarding two scholarships in memory of Dr. Nancy I. Davis. A leadership scholarship of $1500 and a classroom support scholarship of $500.

On July 1, 2017 the Waynesburg Area Chamber of Commerce became the Greene County Chamber of Commerce, serving all of Greene County with over 350 members.

In October of 2018 the Chamber received the Pennsylvania Association of Chamber Professionals Accreditation, the first and only chamber in the state to receive it at that time.  Also in the same month, the Chamber hosted White House appointee, Michelle Christian and the Regional Director of the U.S.D.A. to a Rural Roundtable discussion with members representing various sectors of businesses in the County.