The Reynolda Campus of Wake Forest, which opened in the summer of 1956 upon the institution's move from its original home near Raleigh, is situated on approximately 340 acres. Its physical facilities consist of more than 80 buildings, most of which are of modified Georgian architecture and constructed of Old Virginia brick trimmed in granite and limestone.

The main Quadrangle, Hearn Plaza, is named for Wake Forest’s 12th president, Thomas K. Hearn Jr., who served from 1983 to 2005. Manchester Plaza, named for benefactors and Wake Forest parents Doug Manchester and Elizabeth Manchester, is located on south campus. The Reynolda Gardens complex, consisting of about 128 acres and including Reynolda Woods, Reynolda Village, Reynolda Gardens, and Reynolda House and Museum of American Art, is adjacent to the campus. The Graylyn International Conference Center is nearby.

Wait Chapel, named in memory of Samuel Wait, the first president of the College, seats 2,250. The Wait Chapel tower contains the Janet Jeffrey Carlile Harris Carillon, an instrument of 48 bells. 

Wingate Hall, named in honor of President Washington Manly Wingate, the fourth president of the College, houses the Department for the Study of Religions and the School of Divinity. 

Reynolda Hall, across the upper plaza from Wait Chapel, houses most of the administration, including offices of the President, the Provost, the Dean of the College, the Center for Global Programs and Studies, the Office of Personal and Career Development, and the University Chaplain. It is also home of a large dining facility for the Reynolda Campus. 

The Benson University Center houses the Student Union and is the central hub for student activities, services, and events. The bottom floor of Benson is the home to Pugh Auditorium movie theater, and several food venues including formal dining.  Benson is also home to the LGBTQ Center, located on the second floor.

The Z. Smith Reynolds Library and its Edwin Graves Wilson Wing, named in honor of the Class of 1943 graduate who became a distinguished English professor and administrator at his alma mater, house the main collection of books and documents on the Reynolda Campus. Along with eight floors of open stacks, it has reading and reference rooms for study. 

Carswell Hall,  named in honor of alumnus and benefactor Guy T. Carswell (1922), houses the Department of Communication and a large multimedia lecture area, the Annenberg Forum.

Winston Hall houses the Department of Biology and Salem Hall is home to the Department of Chemistry. Both buildings have laboratories as well as classrooms and special research facilities. The Olin Physical Laboratory houses the physics department.

Harold W. Tribble Hall, named for Wake Forest's 10th president, accommodates primarily humanities departments and the Women’s, Gender, and Sexuality Studies program. It has seminar rooms, a philosophy library, and a multimedia lecture area, DeTamble Auditorium. 

The Museum of Anthropology houses the Department of Anthropology and North Carolina’s only museum dedicated to the study of world cultures. 

The Calloway Center for Mathematics and Computer Science was named in honor of former University Trustee Wayne Calloway ('59, P '95). The building houses the Departments of Mathematics and Statistics and Computer Science in Manchester Hall, and the Departments of Politics and International Affairs, Economics and Sociology in Kirby Hall

Farrell Hall, named for Wake Forest parents and benefactors Michael and Mary Farrell (P '10), broke ground in April 2011 and is home to the School of Business. It hosted its first classes in July 2013 and was formally dedicated in November 2013. 

William B. Greene Jr. Hall, named for alumnus and benefactor Bill Greene ('59), houses the Departments of Psychology, German and Russian, and Romance Languages.

The James R. Scales Fine Arts Center, named for James Ralph Scales, Wake Forest's 11th president, is of contemporary design appropriate to the functions of studio art, theatre, musical and dance performances, and instruction in art history, drama, and music. Off its main lobby is the Charlotte and Philip Hanes Gallery, a facility for special exhibitions named in honor of two benefactors. In the art wing are spacious studios for drawing, painting, sculpture, and printmaking, along with a smaller gallery and classrooms. Adjacent to the art wing is a dance studio for performances and rehearsals. In the theatre wing are design and production areas and two technically complete theatres, the larger of traditional proscenium design and the smaller for experimental ring productions. The music wing contains Brendle Recital Hall, named in honor of former student James David Brendle, for concerts and lectures, classrooms, practice rooms for individuals and groups, and the offices of the Department of Music.

The Worrell Professional Center, named for alumnus and benefactor Eugene T. Worrell ('40), houses the School of Law. Recent additions to Worrell in 2016 provided a new home for instruction in the Department of Health and Exercise Science.

The Wake Forest Wellbeing Center, comprised of the Sutton Center and the Historic W.N. Reynolds Gymnasium, was reimagined and officially dedicated in 2018.  The Sutton Center, named for alumnus and benefactor Ben Sutton ('80, JD '83, P '14, P '16, P '19), provides a large venue for wellbeing, social, and academic gatherings; and Historic W. N. Reynolds Gymnasium, named for a prominent member of the family that helped bring the campus to Winston-Salem, has courts for indoor sports, a swimming pool, and Student Health Services. Adjacent to the Wellbeing Center are sports fields, Kentner Stadium, the Manchester Athletic Center, and the Kenneth D. Miller Center

Alumni Hall, formerly the University Services Building houses University Advancement, the University Police Department, and the Department of Parking and Transportation.

The Porter B. Byrum Welcome Center, named for alumnus and benefactor Porter B. Byrum (JD '42),  is at the entrance to Wake Forest. The building allows prospective students and their families an opportunity to learn more about the University and to meet with admissions staff.

The Barn, built to resemble a North Carolina farm barn, offers opportunities for concerts, performances, and student-sponsored events.

The Wake Forest campus has a wide variety of housing options available to students in residence halls named for alumni, faculty, benefactors, and Wake Forest presidents: Babcock Hall, Bostwick Hall, Collins Hall, Davis Hall, Efird Hall, Huffman Hall, Johnson Hall, Kitchin Hall, Luter Hall, Martin Hall, North Campus Apartments, Palmer Hall, Piccolo Hall, Polo Hall, Poteat Hall, Student Apartments, South Hall, Taylor Hall and the newest Dogwood and Magnolia Residence Halls opened in August 2013 and are coeducational by floor, wing, or apartment. In January 2014, the North Dining facilities opened adjacent to the new residence halls providing several alternative dining options to the north side of campus. In January 2017, Maya Angelou Residence Hall, in honor of the distinguished Wake Forest faculty member and internationally acclaimed poet, opened.  It is also home to the Residence Life and Housing Department.

McCreary Field House, named for alumnus and benefactor Bob McCreary ('61), opened in 2016, providing indoor practice facilities and weightlifting for all of Wake Forest's intercollegiate sports teams.  The Arnold Palmer Golf Complex, named in honor of alumnus, benefactor and life trustee Arnold Palmer (’51), includes the Dianne Daily Golf Learning Center, which opened in 2010 and is named for the coach who has led the women’s golf program since 1988, and the Haddock Golf Center, completed in 2016 and named for Jesse Haddock (’52), who coached the Deacons to three NCAA championships in his 32 years of service.

In January 2017, converted tobacco warehouses became the home of new degree programs in biomedical sciences and engineering. Known as Wake Downtown, this academic extension is located a 13-minute shuttle ride from the Reynolda Campus. That same year, the University opened Wake Washington, a new home of academic operations on DuPont Circle in Washington, D.C.

Wake Forest is the only Top-30 national university to own academic-residential houses in three foreign countries. The University purchased Casa Artom, located on the Grand Canal in Venice and named for beloved medical school professor Dr. Camillo Artom, in 1974. Three years later, it acquired a London facility and named it Worrell House in honor of benefactor Eugene Worrell (’40) and his wife, Anne Worrell. And in 1998, Flow House, named in honor of alumnus, benefactor and University Trustee Victor I. Flow (’52, P ’83) and his wife, Roddy Flow (P ’83), became part of the Wake Forest family.