The campus is 1,232 acres (5 km²) in its entirety, though the main campus is on the western 178 acres (0.7 km²). Despite its urban setting, the campus manages to maintain a surprisingly park-like atmosphere, crossed by two creeks and including the tallest stand of hardwood trees in North America. Overlooking the main campus on the east side are several research units, most notably the Lawrence Berkeley National Laboratory, the Mathematical Sciences Research Institute, and the Lawrence Hall of Science. Much of the rugged upper hill territory is still undeveloped. Residential Halls and administrative buildings spill out into the city of Berkeley, particularly to the south of the campus.

The campus and its surrounding community are home to a number of notable buildings by turn-of-the-20th century campus architect John Galen Howard, his peer Bernard Maybeck (best known for the Palace of Fine Arts), and Maybeck's student, Julia Morgan. Later buildings were designed by prominent architects such as Charles Willard Moore (Haas School of Business) and Joseph Esherick (Wurster Hall).

Very little of the early University of California (c. 1868–1903) remains, with the Victorian Second Empire style South Hall (1873) and Piedmont Avenue (designed by Frederick Law Olmsted) being notable exceptions. What is considered the historic campus today was the eventual result of the 1898 "International Competition for the Phoebe Hearst Architectural Plan for the University of California," funded by the mother of William Randolph Hearst and initially held in the Belgian city of Antwerp (eleven finalists were judged again in San Francisco, 1899). This unprecedented competition came about from one-upmanship between the prominent Hearst and Stanford families of the Bay Area. In response to the founding of Stanford University, the Hearst Family decided to "adopt" the fledgling University of California and develop their own world-class institution. Although a Frenchman, Emile Bénard, won the competition, he disliked the "uncultured" San Francisco atmosphere and resigned. He was replaced by the fourth place winner and the first campus architect, John Galen Howard. Only University House, designed by architect Albert Pissis and then home to the President of the University of California, was placed according to the Bénard plan. (It is today the home of UC Berkeley's Chancellor.)

Much of the older campus is built in the stately Beaux-Arts Classical style, which was regarded as the most cultured, beautiful, and "scientific" style by the cultural establishment at the time of the competition, and thus was the style preferred by John Galen Howard and Phoebe Hearst (who paid his salary). With the support of University President Benjamin Ide Wheeler, Howard designed over twenty buildings, which set the tone for campus up until it post-World War II expansion in the 1950s and 60s. These included the Greek Theatre, the Hearst Memorial Mining Building, Doe Memorial Library, California Hall, Wheeler Hall, (Old) Le Conte Hall, Gilman Hall, Haviland Hall, Wellman Hall, Sather Gate, and the 307-foot Sather Tower (nicknamed "the Campanile" after St. Mark's Campanile in Venice). Buildings he regarded as temporary, non-academic, or not particularly "serious" were designed in shingle or Collegiate Gothic styles; North Gate Hall, Dwinelle Annex, and the Men's Faculty Club (later added to by Maybeck), and Stephens Hall are examples of the former and latter, respectively. Many of his best buildings are on the National Register of Historic Places. Bowles Hall was built in 1928 as California's oldest state-owned dormitory, and is also listed in the National Registry of Historic Places.

John Galen Howard retired in 1924, his support base gone with both Phoebe Hearst's death and President Wheeler's resignation in 1919. William Randolph Hearst, seeking to memorialize his mother, contributed to Howard's resignation by commissioning Bernard Maybeck and Julia Morgan to design a series of dramatic buildings on the southern part of the campus. These were originally to include a huge domed auditorium, a museum, an art school, and a women's gymnasium, all arranged on an eastward esplanade and classically oriented towards the campanile. However, only the Hearst Women's Gymnasium was completed before the Great Depression, at which point Hearst decided to focus on his estate at San Simeon instead.

The dramatic increase in enrollment during the 1950s, 1960s, and 1970s led to the rapid expansion of the campus, beginning with the University's appropriation of the north end of Telegraph Avenue to form Sproul Plaza and headed on its east side by Sproul Hall, a new neoclassical building for the campus administration. However, the administration moved out of Sproul and into California Hall, situated in the heart of campus, after students barricaded themselves in Sproul during the 1964 Free Speech Movement. (Today, Sproul Hall houses Student Services and the Admissions Office, and Sproul Plaza is the center of student activities.) A series of huge Brutalist concrete buildings were also built to provide much-needed housing, lab, office, and classroom space, including Evans Hall, Cory Hall, Wurster Hall, Davis Hall, McCone Hall, Zellerbach Hall, the undergraduate dorms Units 1, 2, and 3, and others.

Dwinelle Hall is another large building on campus, students often get confused in this "Freshman maze."

Gray-green Evans Hall is the tallest instructional building on the campus and houses the offices of faculty in mathematics, statistics, and economics, which once included former Assistant Professor of Mathematics Ted Kaczynski—famously known as the Unabomber. Along with Wurster Hall, Evans Hall is widely considered to be one of the less attractive buildings on campus. The most recent campus development plan lists Evans Hall as a candidate for demolition within the next fifteen years. Cory Hall, the electrical engineering building, was the site of two attacks by the Unabomber in 1982 and 1985. Its neighbor Soda Hall (computer science), is one of the few classroom buildings on campus with showers. It was completed in August 1994, at the cost of $35.5 million, raised entirely from private gifts.

Recent developments include the new Jean Hargrove Music Library and the completion of funding for the planned Chang-Lin Tien Center, which will be the fourth free-standing music library and the first free-standing building devoted to East Asian Studies, respectively, in the United States.