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Old Main, originally known as University Hall and Main Hall, is a historic university building at the University of South Dakota. Originally built in 1883, it is the oldest building on campus, despite having been rebuilt after an 1893 fire. It has been listed on the National Register of Historic Places since 1973.

The Dean Belbas Center, referred to simply as the Belbas Center or the Old Armory, is a historic building on the University of South Dakota campus. Originally constructed in 1905 as an armory, it has been repurposed multiple times over the years; it has served as a barracks, an athletics building, and a recreation ground. Currently, the admissions, registrar, and financial aid offices are located there.

The National Music Museum: America's Shrine to Music & Center for Study of the History of Musical Instruments (NMM) is a musical instrument museum in Vermillion, South Dakota, United States. It was founded in 1973 on the campus of the University of South Dakota. The NMM is recognized as "A Landmark of American Music" by the National Music Council.The NMM's renowned collections, which include American, European, and non-Western instruments from a wide breadth cultures and historical periods, are among the world's most inclusive. They contain many of the earliest, best preserved, and historically most Western important instruments known to survive. The quality and scope of the NMM has earned it international recognition.In August 2023, the museum re-opened its permanent exhibitions following a multi-year renovation and reinstallation. Alongside a modern addition to the historic Carnegie Library building, the new galleries offer over 16,000 square feet of displays showcasing the way musical instruments, across time and space, a part of our lives.The museum's current director is Dwight Vaught.

Vermillion (Lakota: Waséoyuze; "The Place Where Vermilion is Obtained") is a city and the county seat of Clay County. It is in the southeastern corner of South Dakota, United States, and is the state's 12th-most populous city. According to the 2020 Census, the population was 11,695. The city lies atop a bluff near the Missouri River. The area has been home to Native American tribes for centuries. French fur traders first visited in the late 18th century. Vermillion was founded in 1859 and incorporated in 1873. The name refers to the Lakota name: wa sa wak pa'la (red stream). Home to the University of South Dakota, Vermillion has a mixed academic and rural character: the university is a major academic institution for the state, with its only law and medical schools and its only AACSB-accredited business school. Major farm products include corn, soybeans, and alfalfa.

The University of South Dakota (USD) is a public research university in Vermillion, South Dakota. Established by the Dakota Territory legislature in 1862, 27 years before the establishment of the state of South Dakota, USD is the flagship university for the state of South Dakota and the state's oldest public university. It occupies a 274 acres (1.11 km2) campus located in southeastern South Dakota, approximately 63 miles (101 km) southwest of Sioux Falls, 39 miles (63 km) northwest of Sioux City, Iowa, and north of the Missouri River. The university is home to South Dakota's only medical school and law school. It is also home to the National Music Museum, with over 15,000 American, European, and non-Western instruments. USD is governed by the South Dakota Board of Regents, and its president is Sheila Gestring. The university has been accredited by the North Central Association of College and Schools since 1913. It is classified among "R2: Doctoral Universities – High research activity".University of South Dakota's alumni include a total of 17 Truman Scholars, 12 Rhodes Scholars, and 1 Nobel Laureate (Ernest Lawrence '22, 1939 Nobel Prize in Physics). The athletic teams compete in the NCAA's Division I as members of The Summit League, except football, which competes in the Missouri Valley Football Conference.

The University of South Dakota School of Law also known as University of South Dakota Knudson School of Law or USD Law in Vermillion, South Dakota, United States, is a professional school of the University of South Dakota and the only law school in the state of South Dakota. Established in 1901, by U.S. Ambassador Bartlett Tripp and U.S. Senator Thomas Sterling. The law school is home to approximately 168 students and has more than 3,000 alumni. With 168 J.D. candidates, it is currently the second-smallest law school and smallest public law school student population among the American Bar Association accredited law schools.The University of South Dakota School of Law has produced 8 Governors of South Dakota including as well as other key figures important to the development of the state, many judges of the South Dakota Supreme Court and the U.S. District Court for the District of South Dakota, 13 members of the U.S. Congress, 19 Attorneys General of South Dakota, and 14 U.S. Attorneys for the District of South Dakota, earning it the nickname "the Alma Mater of the State."

Inman House, formerly known as the University of South Dakota Alumni House, is a historic American building in Vermillion, South Dakota. It is currently a private residence for the President of the University of South Dakota. It was added to the National Register of Historic Places in 1976.

The University of South Dakota Sanford School of Medicine is the medical school of the University of South Dakota. It offers the Doctor of Medicine, master's and PhD degrees in biomedical sciences, and an MD–PhD. The dean of the school is Dr. Tim Ridgway. The school has four campuses (Vermillion, Sioux Falls, Rapid City, and Yankton) and several additional farm- and rural-focused sites through its Frontier And Rural Medicine (FARM) program. The FARM sites are in Milbank, Mobridge, Parkston, Platte, Winner, Pierre, Spearfish, and Vermillion.In 2016, 71 students were accepted of 859 applicants. More than most medical schools, Sanford School of Medicine recruits students from and trains doctors for rural locations.

Prentis Park is a city park in Vermillion, South Dakota. It is a rectangular 20-acre (8.1 ha) park located on the block bounded by Plum Street, Main Street, Clark Street, and Prentis Avenue. It was listed on the National Register of Historic Places in 2001.

The First Methodist Episcopal Church in Vermillion, South Dakota is a historic church at 14-16 North Dakota Street. It has also been known as First United Methodist Church. It was built during 1927-29 and was added to the National Register in 2004.It was deemed significant "as a well preserved example of a Late Gothic Revival style and a sub-type termed castellated or parapeted. It is an excellent example of this style in South Dakota."

The Gunderson House is a historic residence located at 24 South Harvard Street in Vermillion, South Dakota. It was listed on the National Register of Historic Places in 2001, due to being a notable example of Queen Anne architecture in Clay County.The house's builder, Harvey Gunderson, moved to Dakota Territory by way of Wisconsin in 1869 and purchased a 160-acre farm in the Vermillion area. In 1895, he built this house for his family, which at the time was still on the outskirts of town. Today, Gunderson House sits near the center of Vermillion, borders the Forest Avenue Historic District, and is a few blocks from the University of South Dakota. It is still a private residence.

The Sanford Coyote Sports Center is an indoor arena located on the campus of the University of South Dakota (USD) in Vermillion, South Dakota. The facility opened in 2016 and hosts the university's men's basketball, women's basketball, and women's volleyball teams. It has a seating capacity of 6,000. The center is named after a major supporter of the athletic program, Sanford Health, which donated $20 million to help with construction of the facility.The facility is connected to the DakotaDome, which had previously been home to all of the new arena's main tenants and remains home to Coyote football, track & field, and swimming & diving. In addition to the main arena, it houses athletic department offices, training and meeting facilities, two practice courts, a video production room that controls display boards at all USD sports venues, and an area set aside for future expansion of the USD occupational and physical therapy programs. Additionally, it includes luxury boxes that allow their fans to watch events at both the Sanford Coyote Sports Center and DakotaDome.The first event in the new arena was a Coyote volleyball match against North Dakota on August 30, 2016, with the Coyotes winning 3–1 by sets.