On December 17, 1974, the voters of Mississippi Count approved the establishment of a community college district and the levying of a three mill tax to finance construction of the new campus.  The State Board of Higher Education and the State Legislature had previously approved establishment of the institution.  Governor Dale Bumpers appointed a nine member Board of Trustees who began a search for a President for the institution.  Dr. Harry V. Smith, selected as the first President of the College, began service in February 1975, and served unto October 1, 1983, when he was succeeded by Dr. John P. Sullins.  An administrative team and faculty were assembled, and on August 25, 1975, classes began for the first time in renovated, temporary facilities located in the former Sudbury Elementary School at 200 South Lake Street in Blytheville.  Approximately 800 students enrolled for credit the first term.  Non-credit community service courses began with an additional 500 students in the spring term.  In February 1976, the Board of Trustees purchased 80 acres of land for construction on South Highway 61.

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On April 29, 1977, United States Vice President Walter F. Mondale announced that the College had been awarded a $6.3 million federal grant to build the nation's first solar photovoltaic prototype facility.  An additional $500,000 was received and combined with the $6.3 million grant and a $2.5 million county bond issue.  The campus on South Highway 61 was occupied in August 1980.  In May 1980, the College was notified that it had been accredited and had attained membership in the North Central Association of Colleges and Schools.

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Cotton Boll Technical Institute first opened its doors on November 14, 1966.  At that time approximately fifty students enrolled.  The school was housed in a single 26,462 square foot building surrounded by cotton fields off Interstate 55 at Burdette.

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With more than 60 years of history between them, Cotton Boll Technical Institute merged with Mississippi County Community College on July 1, 2003, to become Arkansas Northeastern College.  This merger expanded the technical opportunities offered by the College as well as created the expansion of physical facilities.

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Today, ANC enrolls students at the main campus in Blytheville, as well as the Leachville Center and the Osceola Center.  Additionally, hundreds of students are served each semester through the College's non-credit and adult education programs.

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Following the construction of the initial Main Campus building in 1980, the College later added the B and C Wings, the D Building which houses the Sunshine Grille and Sun Room, the Adams/Vines Building and Library, Statehouse Hall, and the NIBCO Children's Care Center, the Briggs/Sebaugh Wellness Center, the Angela Wren Allied Health enter, and College's newest facility, the ANC Center for Allied Technologies which moved the operations of the Harry L. Crisp Center, the Burdette Center, and the ACME Center to the Main Campus.

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Since its inception, five individuals have led the institution.  Dr. Smith, the first president, left the College in 1983, and was succeeded by Dr. John P. Sullins who served in that capacity for 22 years.  Dr. Robert Myers became the College's third president on January 1, 2005, and served until July 2012, at which time June Walters was named Interim President.  on January 1, 2013, Dr. James Shemwell assumed the position of President of Arkansas Northeastern College and served until June 30, 2023.  Dr. Christopher Heigle was named ANC's fifth President on July 1, 2023.