William M. Branham was born near Burkesville, Kentucky, on April 6, 1909, the son of Charles and Ella Harvey Branham, and the oldest of ten children. He claimed that at his birth, a "Light come [sic] whirling through the window, about the size of a pillow, and circled around where I was, and went down on the bed". Branham told his publicist Gordon Lindsay that he had mystical experiences from an early age; and that at age three he heard a "voice" speaking to him from a tree telling him "he would live near a city called New Albany". According to Branham, that year his family moved to Jeffersonville, Indiana. Branham also said that when he was seven years old, God told him to avoid smoking and drinking alcoholic beverages. Branham stated he never violated the command.

Following his June tent meeting, Branham's supporters helped him organize a new church, the Branham Tabernacle, in Jeffersonville. Branham served as pastor from 1933 to 1946. The church flourished at first, but because of the Great Depression it was often short of funds and Branham served without compensation, and worked as a game warden to earn an income. Branham believed the stagnation of the church's growth was a punishment from God for his failure to embrace Pentecostalism. Branham married Amelia Hope Brumbach (b. July 16, 1913) in 1934, and they had two children; william "Billy" Paul Branham (b. September 13, 1935) and Sharon Rose Branham (b. October 27, 1936). Branham's wife died on July 22, 1937, and their daughter died four days later (July 26, 1937), shortly after the Ohio River flood of 1937. Branham interpreted their deaths as God's punishment for his continued resistance to holding revivals for the Oneness Pentecostals.

At 19, Branham left home seeking a better life; he traveled to Phoenix, Arizona, where he worked for two years on a ranch and began a successful career in boxing. He returned to Jeffersonville when his brother died in 1929. Branham had no experience with religion as a child; he said the first time he heard a prayer was at his brother's funeral. Soon after, while working for the Public Service Company of Indiana, Branham was almost killed when he was overcome by gas. While recovering from the accident, he said he again heard a voice leading him to begin seeking God. He began attending a local Independent Baptist church, the First Pentecostal Baptist Church of Jeffersonville, where he converted to Christianity. Six months later he was ordained as an Independent Baptist minister. His early ministry was an "impressive success"; he quickly attracted a small group of followers, who helped obtain a tent in which he could hold a revival.

Branham issued a series of prophecies during his ministry. He claimed to have had a prophetic revelation in June 1933 that predicted seven major events would occur before the Second Coming of Christ. His followers believe he predicted several events, including the 1937 Ohio River Flood. In 1964, Branham said judgement would strike the west coast of the United States and that Los Angeles would sink into the ocean; his most dramatic prediction. Following both the 1933 and 1964 prophecies, Branham predicted the rapture would happen by 1977 and would be preceded by various worldwide disasters, the unification of denominational Christianity, and the rise-to-power of the Roman Catholic Pope. Peter Duyzer, among other of Branham's critics, wrote that none of Branham's prophecies came true and that they were all made after the fact. Weaver wrote that Branham tended to embellish his predictions over time. Branham's followers believe his prophecies came true, or will do so in the Future.

At the time of Branham's conversion, The First Pentecostal Baptist Church of Jeffersonville was a nominally Baptist church that observed some Pentecostal doctrines, including Divine healing. As a result, he may have been exposed to some Pentecostal teachings from his conversion. He was first exposed to a Pentecostal denominational church in 1936, which invited him to join, but he refused.

Branham is known for his role in the healing revivals that occurred in the United States in the 1940s and 1950s, and most participants in the movement regarded him as its initiator. Christian Writer John Crowder described the period of revivals as "the most extensive public display of miraculous power in modern history". Some, like critic and radio personality Hank Hanegraaff, rejected the entire healing revival as a hoax and condemned the subsequent evangelical and Charismatic movements as a cult. Divine healing is a tradition and belief that has been held by a majority of Christians in all ages but became increasingly associated with Evangelical Protestantism. The fascination of most of American Christianity with Divine healing played a significant role in the popularity and inter-denominational nature of the revival movement.

Branham married Meda Marie Broy in 1941, and together they had three children; Rebekah (b. 1946), Sarah (b. 1950), and Joseph (b. 1955).

His first revival meetings were held over 12 days during June 1946 in St. Louis. His first campaign manager, W.E. Kidston, was Editor of The Apostolic Herald and had many contacts in the Pentecostal movement. Kidston was instrumental in helping organize Branham's early revival meetings. Time magazine reported on his St. Louis campaign meetings; according to the article, Branham drew a crowd of over 4,000 sick people who desired healing and recorded him diligently praying for each. Branham's fame began to grow as a result of the publicity and reports covering his meetings. Following the St. Louis meetings, Branham launched a tour of small Oneness Pentecostal churches across the Midwest and southern United States, from which stemmed reports of healing and one report of a resurrection.

Branham faced criticism and opposition from the early days of the healing campaign. According to Kydd, Branham evoked strong opinions from people with whom he came into contact; "most people either loved him or hated him". In 1947, Rev. Alfred Pohl, a minister in Saskatchewan, Canada, stated that many people Branham pronounced as healed later died. A year later, W. J. Taylor, a district superintendent with the Pentecostal Assemblies of Canada, raised the same concern and asked for a thorough investigation. Taylor presented evidence that claims of the number of people healed were vastly overestimated. He stated; "there is a possibility that this whole thing is wrong". The number of people who claimed to be healed in Branham's campaign meetings "is impossible to approximate" and the numbers vary greatly between sources. According to Historian Ronald Kydd, by watching films of the revival meetings, "the viewer would assume almost everyone was healed" but the results proved otherwise the few times follow-up was made. No consistent record of follow-ups was made, making analysis of the claims difficult to subsequent researchers. Pentecostal Historian Walter Hollenweger said, "very few were actually healed". Some attendees of Branham's meetings believed the healings were a hoax and accused him of selectively choosing who could enter the prayer line. Many people left his meetings disappointed after finding Branham's conviction that everyone in the audience could be healed without being in the prayer line proved incorrect. Branham generally attributed the failure of supplicants to receive healing to their lack of faith

Branham told audiences the angel that commissioned his ministry had given him two signs by which they could prove his commission. He described the first sign as vibrations he felt in his hand when he touched a sick person's hand, which communicated to him the nature of the illness but did not guarantee healing. The second sign he described to his audiences was a gift of knowledge; This second sign did not appear in his campaigns until after his recovery in 1948, and was used to "amaze tens of thousands" at his meetings. According to Bosworth, this gift of knowledge allowed Branham "to see and enable him to tell the many events of [people's] lives from their childhood down to the present". This caused many in the healing revival to view Branham as a "seer like the old testament prophets". Branham amazed even fellow Evangelists, which served to further push him into a legendary status in the movement. Branham's audiences were often awestruck by the events during his meetings. At the peak of his popularity in the 1950s, Branham was widely adored and "the neo-Pentecostal world believed Branham to be a prophet to their generation".

Branham was the "initiator of the post-World War II healing revival" and, along with Oral Roberts, was one of its the most revered Leaders. Branham is most remembered for his use of the "sign-gifts" that awed a generation of his followers. The many revivalists who attempted to emulate Branham during the 1950s spawned a generation of prominent Charismatic ministries. Branham has been called the "principle Architect of restorationist thought" of the "new charismatics". The Charismatic view that the Christian church should return to a form like that of the early church has its roots in Branham's teachings during the healing revival period. The belief is widely held in the modern Charismatic movement, and the legacy of his restorationist teaching and ministering style is evident throughout televangelism and the Charismatic movement.

In January 1951, U.S. Congressman william Upshaw, who had been crippled for 59 years as the result of an accident, said he was miraculously healed and had regained the ability to walk in a Branham meeting, further fueling Branham's fame. Upshaw sent a letter describing his healing claim to each member of Congress. Among the widespread media reports was a story in the Los Angeles Times that described it as "perhaps the most effective healing testimony this generation has ever seen". Upshaw died in November 1952.

In 1955, Branham's campaigning career began to slow following financial setbacks. Even after he became famous, Branham continued to wear inexpensive suits and refused large salaries; he was not interested in amassing wealth as part of his ministry and was reluctant to solicit donations during his meetings. During the early years of his campaigns, donations had been able to cover costs but from 1955, donations failed to cover the costs of three successive campaigns, one of which incurred a $15,000 deficit. Some of Branham's Business associates thought he was partially responsible because of his lack of interest in the financial affairs of the campaigns and tried to hold him personally responsible for the debt. Branham briefly stopped campaigned and said he would have to take a job to repay the debt but the Full Gospel Business Men's Fellowship International ultimately paid it. The Full Gospel Businessmen became the primary financier for Branham's campaign meetings as the Pentecostal denominations began to withdraw their financial support.

Among Branham's emulators was Jim Jones, the founder and leader of the Peoples Temple. Seeking a means to catapult his fame and earn followers, he invited Branham to a self-organized religious convention held at the Cadle Tabernacle auditorium in Indianapolis from June 11 to 15, 1956. To draw the crowds he was seeking, Jones needed a religious headliner and arranged to share the platform with Branham. Branham critics Peter Duyzer and John Collins reported that Branham "performed numerous miracles", drawing a crowd of 11,000. Jones later became known for the mass murder and suicide at Jonestown in November 1978. According to Collins, Jim Jones and Paul Schäfer were influenced to move to South America by Branham's 1961 prophecy concerning Armageddon. Collins and Duyzer concluded that Jones did not "see eye-to-eye" with Branham and that Jones believed he was dishonest.

Annihilationism is a pre-existing doctrinal conflict within Pentecostalism that originated at latest in the time of Charles Fox Parham, who was a supporter of the doctrine, but not all sects accepted the teaching. Prior to 1957, Branham taught a doctrine of eternal punishment in hell. By 1957, however, he adopted an annihilationist position in keeping with Parham's teachings. He began promoting the belief that punishment of the damned in Hell would not last for eternity and that eventually the damned would cease to exist. He believed that "eternal life was reserved only for God and his children" In 1960, Branham claimed the Holy Spirit had revealed this doctrine to him as one of the end-time mysteries. Promoting annihilationism led to the alienation of Pentecostal groups that had rejected Parham's teaching on the subject.

Branham first spoke about original sin in 1958; he rejected the orthodox view of the subject and hinted at his own belief in a hidden meaning to the story. In later years, he made his opinion concerning the sexual nature of the fall explicitly known. Weaver wrote that Branham may have become acquainted with serpent seed doctrine through his Baptist roots; Daniel Parker, an American Baptist minister from Kentucky, promulgated a similar doctrine in the mid-1800s. According to Pearry Green, Branham's teaching on the serpent seed doctrine was viewed by the broader Pentecostal movement as the "filthy doctrine ... that ruined his ministry". No other mainstream Christian group held a similar view; Branham was widely criticized for spreading the doctrine. His followers, however, view the doctrine as one of his greatest revelations.

In 1960, Branham preached a series of sermons on the seven church ages based on chapters two and three of the Book of Revelation. The sermons closely aligned with the teachings of C. I. Scofield and Clarence Larkin, the leading proponents of dispensationalism in the preceding generation. Like Larkin and Scofield, Branham said each church represents a historical age, and taught that the angel of each age was a significant church figure. The message included the description of a messenger to the Laodicean Church age, which Branham believed would immediately precede the rapture. The characteristics of the Laodicean age resemble those of the modern era. Branham claimed the messenger to this last age would come in the spirit of Elijah the prophet and cited the Book of Malachi 4:5-6 as the basis for claiming the Elijah spirit would return. His belief in a "seventh church age messenger" came from his interpretation of the Book of Revelation 3:14-22.

Despite his rejection by the growing Charismatic movement, Branham's followers became increasingly dedicated to him during his later life; some even claimed he was the Messiah. Branham quickly condemned their belief as heresy and threatened to stop ministering but the belief persisted. Many followers moved great distances to live near his home in Jeffersonville and subsequently set up a colony in Arizona following Branham's move to Tucson in 1962. Branham lamented their actions and worried that a cult was potentially being formed among his most fanatical followers.

Branham regarded his 1963 series of sermons on the Seven Seals as a highlight of his ministry. According to Weaver, they were primarily "a restatement of the dispensationalism espoused in the sermons on the seven church ages". The sermons focused on the Book of Revelation 6:1-17, and provided an interpretation of the meaning of each of the seals. Branham claimed the sermons were inspired through an Angelic visitation.

The initial reaction of Branham's followers to his death, which also stunned the Pentacostal world, was one of shock. His funeral was held on December 29, 1965, but his burial was delayed. His body was finally buried on April 11, 1966; Easter Monday. Most eulogies only tacitly acknowledged Branham's controversial teachings, focusing instead on his many positive contributions. Gordon Lindsay's eulogy stated that Branham's death was the will of God and privately he accepted the interpretation of Kenneth Hagin, who claimed to have prophesied Branham's death two years before it happened. According to Hagin, God revealed that Branham was teaching false doctrine and God was removing him because of his disobedience.

In the confusion immediately following Branham's death, expectations that he would rise from the dead developed among his followers. Most believed he would have to return to fulfill a vision he had regarding Future tent meetings. Weaver attributed the belief in Branham's imminent resurrection to Pearry Green, though Green denied it. Even Branham's son Billy Paul seemed to expect his father's resurrection and indicated as much in messages sent to Branham's followers, in which he communicated his expectation for Easter 1966. The expectation of his resurrection remained strong into the 1970s, in part based on Branham's prediction of the rapture occurring by 1977. Following 1977, some of his followers abandoned his teachings.

Though Branham is no longer widely known outside of Pentecostalism, his legacy continues today. Summarizing the contrasting views held of Branham, Kydd stated, "Some thought he was God. Some thought he was a dupe of the devil. Some thought he was an end-time messenger sent from God, and some still do." Followers of Branham's teachings can be found around the world; in 1986, there were an estimated 300,000 followers. In 2000, the william Branham Evangelical Association had missions on every inhabited continent—with 1,600 associated churches in Latin America and growing missions across Africa. In 2018, Voice of God Recordings claimed to serve Branham-related support material to about two million people though the william Branham Evangelical Association. Branham claimed to have made over one million converts during his campaign meetings.