He was a descendant of one of the First Families of Virginia. His ancestors included planter John Rolfe and his wife Pocahontas, William Byrd II of Westover Plantation, who established Richmond, and Robert "King" Carter, a colonial governor. He was the brother of Virginia Governor and U.S. Senator Harry Flood Byrd, a dominant figure in Virginia Democratic Party between the 1920s and 1960s.

Byrd attended the University of Virginia before financial circumstances inspired his transfer to the United States Naval Academy in 1912. He learned to fly in World War I during his tour with the United States Navy. He developed a passion for flight, and pioneered many techniques for navigating airplanes over the open ocean including drift indicators and bubble sextants. His expertise in this area resulted in his appointment to plan the flight path for the U.S. Navy's 1919 transatlantic crossing. Of the three flying boats that attempted it, only Albert Read's NC-4 aircraft completed the trip, becoming the first ever transatlantic flight.

On May 9, 1926, Byrd and pilot Floyd Bennett attempted a flight over the North Pole in a Fokker F-VII Tri-motor called the Josephine Ford. This flight went from Spitsbergen (Svalbard) and back to its take-off airfield. Byrd claimed to have reached the Pole. This trip earned Byrd widespread acclaim, including being received the Medal of Honor and enabled him to secure funding for subsequent attempts to fly over the South Pole.

From 1926 until 1996, there were doubts, defenses, and heated controversy about whether or not Byrd actually reached the North Pole. In 1958 Norwegian-American aviator and explorer Bernt Balchen cast doubt on Byrd's claim on the basis of his extensive personal knowledge of the airplane's speed. In 1971 Balchen speculated that Byrd had simply circled aimlessly while out of sight of land.

The 1996 release of Byrd's diary of the May 9, 1926 flight revealed erased (but still legible) sextant sights that sharply differ with Byrd's later June 22 typewritten official report to the National Geographic Society. Byrd took a sextant reading of the Sun at 7:07:10 GCT. His erased diary record shows the apparent (observed) solar altitude to have been 19°25'30", while his later official typescript reports the same 7:07:10 apparent solar altitude to have been 18°18'18". On the basis of this and other data in the diary, Dennis Rawlins concluded that Byrd steered accurately, and flew about 80% of the distance to the Pole before turning back because of an engine oil leak, but later falsified his official report to support his claim of reaching the pole.

Accepting that the conflicting data in the typed report's flight times indeed require both northward and southward groundspeeds greater than the flight's 85 mph airspeed, a remaining Byrd defender posits a westerly-moving anti-cyclone that tailwind-boosted Byrd's groundspeed on both outward and inward legs, allowing the distance claimed to be covered in the time claimed. (The theory is based on rejecting handwritten sextant data in favor of typewritten alleged dead-reckoning data.) This suggestion has been refuted by Dennis Rawlins who adds that the sextant data in the long unavailable original official typewritten report are all expressed to 1", a precision not possible on Navy sextants of 1926 and not the precision of the sextant data in Byrd's diary for 1925 or the 1926 flight, which was normal (half or quarter of a minute of arc). Some sources claim that Floyd Bennett and Byrd later revealed, in private conversations, that they did not reach the pole. One source claims that Floyd Bennett later told a fellow pilot that they did not reach the pole. It is also claimed that Byrd confessed his failure to reach the North Pole during a long walk with Dr. Isaiah Bowman in 1930.

Considering that Byrd and Bennett probably didn't reach the North Pole, it is extremely likely that the first flight over the Pole was the flight of the airship Norge in May 1926 with its crew of Roald Amundsen, Umberto Nobile, Oscar Wisting, and others. This flight went from Spitsbergen (Svalbard) to Alaska nonstop, so there is little doubt that they went over the North Pole. Amundsen and Wisting had both been members of the first expedition to the South Pole, December 1911.

Byrd was one of several aviators who attempted to win the Orteig Prize in 1927 for making the first nonstop flight between the United States and France. His flight was sponsored by department-store magnate Rodman Wanamaker, an early visionary of Trans-Atlantic commercial flight. Once again Byrd named Floyd Bennett as his chief pilot, with support from Bernt Balchen, Bert Acosta, and George Noville. During a practice takeoff with Tony Fokker at the controls and Bennett in the co-pilots seat, the Fokker Trimotor airplane, America, crashed, severely injuring Bennett and slightly injuring Byrd. As the plane was being repaired, Charles Lindbergh won the prize. But Byrd continued with his quest, naming Balchen to replace Bennett as chief pilot. Byrd, Balchen, Acosta, and Noville flew from Roosevelt Field East Garden City, New York on June 29, 1927. Arriving over France, cloud cover prevented a landing in Paris; they returned to the coast of Normandy, crash-landing near the beach at Ver-sur-Mer without fatalities on July 1, 1927.

In 1928, Byrd began his first expedition to the Antarctic involving two ships, and three airplanes: a Ford Trimotor called the Floyd Bennett (named after the recently deceased pilot of Byrd's previous expeditions); a Fairchild FC-2W2, NX8006, built 1928, named "Stars And Stripes" (now displayed at the Virginia Aviation Museum, on loan from the National Air and Space Museum); and a Fokker Universal monoplane called the Virginia (Byrd's birth state). A base camp named "Little America" was constructed on the Ross Ice Shelf and scientific expeditions by snowshoe, dog-sled, snowmobile, and airplane began. Photographic expeditions and geological surveys were undertaken for the duration of that summer, and constant radio communications were maintained with the outside world. After their first winter, their expeditions were resumed, and on November 28, 1929, the famous flight to the South Pole and back was launched. Byrd, along with pilot Bernt Balchen, co-pilot/radioman Harold June, and photographer Ashley McKinley, flew the Ford Trimotor to the South Pole and back in 18 hours, 41 minutes. They had difficulty gaining enough altitude, and they had to dump empty gas tanks, as well as their emergency supplies, in order to achieve the altitude of the Polar Plateau. However, the flight was successful, and it entered Byrd into the history books. After a further summer of exploration, the expedition returned to North America on June 18, 1930. A 19 year-old American Boy Scout, Paul Allman Siple, was chosen to accompany the expedition. Unlike the 1926 flight, this expedition was honored with the gold medal of the American Geographical Society.

Byrd, by then an internationally recognized, pioneering American polar explorer and aviator, served for a time as Honorary National President (1931–1935) of Pi Gamma Mu, the international honor society in the social sciences. In 1928, he carried the Society's flag during a historic expedition to the Antarctic to dramatize the spirit of adventure into the unknown, characterizing both the natural and social sciences.