Dwight Moody was born in Northfield, Massachusetts to a large family. His father, a small farmer and stonemason, was an alcoholic and died at the age of 41 when Dwight was only four years old. He had five older brothers and a younger sister, with an additional twin brother and sister born one month after his father's death. His mother struggled to support the family, but even with her best effort, some of her children had to be sent off to work for their room and board. Dwight too was sent off, where he went he received cornmeal porridge and milk, three times a day. He complained to his mother, but when she found out that he had all that he wanted to eat, she sent him back. Even during this time, she continued to send them to church. Together with his eight siblings he was raised in the Unitarian church. His oldest brother ran away and was not heard from by the family until many years later.

When Moody turned 17, he moved to Boston to (after many job rejections) work in his uncle's shoe store. One of his uncle's requirements was that Moody attend the Congregational Church of Mount Vernon where Dr. Edward Norris Kirk was pastor. In April 1855 Moody was then converted to evangelical Christianity when his Sunday school teacher, Edward Kimball talked to him about how much God loved him. His conversion sparked the start of his career as an evangelist. However his first application for church membership, in May 1855, was rejected. He was not received as a church member until May 4, 1856. As his teacher, Mr. Edward Kimball, stated:

Moody moved to Chicago, Illinois in September, 1856, where he joined the Plymouth Congregational Church, and began to take an active part in the prayer meetings. In the spring of 1857, he began to minister to the welfare of the sailors in Chicago's port, then gamblers and thieves in the saloons. A contemporary witness, William Reynolds, recalled a few years later:

After the Civil War started, he was involved with the U.S. Christian Commission of the YMCA, and paid nine visits to the battle-front, being present among the Union soldiers after the conflicts of Shiloh, Pittsburgh Landing, and Murfreesboro, and ultimately entered Richmond with the army of General Grant. He married Miss Emma C. Revell, on August 28, 1862, with whom he had a daughter, Emma Reynolds Moody, and two sons, William Revell And Paul Dwight Moody.

The growing Sunday School congregation needed a permanent home, so Moody started a church in Chicago, the Illinois Street Church.

In June 1871, Moody met Ira D. Sankey, the Gospel singer, with whom he soon partnered. In October the Great Chicago Fire destroyed his church, his home, and the dwellings of most of his members. His family had to flee for their lives, and, as Mr. Moody said, he saved nothing but his reputation and his Bible. His church was rebuilt within three months at a near-by location as the Chicago Avenue Church. His lay follower William Eugene Blackstone was a prominent American Zionist.

In the years after the fire, Moody's wealthy Chicago supporter J.A. Farwell attempted to persuade him to make his permanent home in Chicago, offering to build Moody and his family a new house. But the now-famous Moody, also sought by supporters in New York, Philadelphia and elsewhere, chose the tranquil farm he had purchased next door to his birthplace in Northfield, MA. He felt he could better recover from his lengthy and exhausting preaching trips in a rural setting. Northfield became an important location in evangelical Christian history in the late 19th century as Moody organized summer conferences which were led and attended by prominent Christian preachers and evangelists from around the world. It was also in Northfield where Moody founded three schools which later merged into today's Northfield Mount Hermon School.

It was while on a trip to England in Spring of 1872 that he became well known as an evangelist. Some have claimed he was the greatest evangelist of the 19th century. He preached almost a hundred times and came into communion with the Plymouth Brethren. On several occasions he filled stadiums of 2,000 to 4,000 capacity. In the Botanic Gardens Palace, a meeting had between 15,000 to 30,000 people.

This turnout continued throughout 1874 and 1875, with crowds of thousands at all of his meetings. During his visit to Scotland he was helped and encouraged by Andrew A. Bonar. The famous London Baptist preacher, Charles Spurgeon invited him to speak and promoted him as well. When he returned to the United States, crowds of 12,000 to 20,000 were just as common as in England. President Grant and some of his cabinet attended a meeting on January 19, 1876. His evangelistic meetings were held from Boston to New York, throughout New England and as far as San Francisco, and other West coast towns from Vancouver to San Diego.

Moody aided in the work of cross-cultural evangelism by promoting "The Wordless Book", a teaching tool that had been invented by Charles Spurgeon in 1866. In 1875 he added a fourth color to the design of the three-color evangelistic device: gold - to "represent heaven". This "book" has been and is still used to teach uncounted thousands of illiterate people - young and old - around the globe about the Gospel message.

Dwight L. Moody visited Britain with Ira D. Sankey, Moody preaching and Sankey singing. Together they published books of Christian hymns. In 1883 they visited Edinburgh and raised £10,000 for the building of a new home for the Carrubbers Close Mission. Moody later preached at the laying of the foundation stone for what is one of the few buildings on the Royal Mile which continues to be used for its original purpose and is now called the Carrubbers Christian Centre.

Moody greatly influenced the cause of cross-cultural Christian missions after he met the pioneer missionary to China, Hudson Taylor. He actively supported the China Inland Mission and encouraged many of his congregation to volunteer for service overseas.

His influence was felt among Swedes despite the fact that he was of English heritage, never visited Sweden or any Scandinavian country, and never spoke a word of the Swedish language. Nevertheless, he became a hero revivalist among Swedish Mission Friends in Sweden and America.

News of Moody’s large revival campaigns in Great Britain from 1873—1875 traveled quickly to Sweden, making “Mr. Moody” a household name in homes of many Mission Friends. Moody’s sermons published in Sweden were distributed in books, newspapers, and colporteur tracts, and led to the spread of Sweden’s “Moody fever” from 1875—1880.

He preached his last sermon on November 16, 1899 in Kansas City, Kansas. Becoming ill, he returned home by train to Northfield. During the preceding several months, friends had observed he had added some 30 pounds to his already ample frame. Although his illness was never diagnosed, it has been speculated that he suffered congestive heart failure. He died on December 22, surrounded by family. Already installed by Moody as leader of his Chicago Bible Institute, R. A. Torrey succeeded Moody as its president. Ten years after Moody's death, the Chicago Avenue Church was renamed The Moody Church in his honor, and the Chicago Bible Institute was likewise renamed Moody Bible Institute.