Edwin Delmont Kelley was born the second son of Obadiah and Mary Kelley on June 18, 1846, in Clarendon, Vermont. His father's family were Quakers, and their spiritual practices influenced him at a young age. His family later moved to Weston, Vermont, where he grew up. Kelley had a vigorous intellect as a child, with the ability to read and do arithmetic at three years of age. In the following years, he displayed a propensity for language, excelling in French, Latin, and Greek. He then went on to study at the University of Michigan in Ann Arbor. Eugene, his older brother, enrolled with Edwin but soon left and joined the Union Army during the American Civil War. During the summer of 1864, Eugene was killed.

On December 4, 1864, Sewall Mason Osgood, an American Baptist Missionary Union (ABMU) missionary from Burma, came to Ann Arbor, preached a sermon, and called for advancement in Burma's mission efforts. The talk made a lasting impression on Kelley.

In June 1866, he graduated from the University of Michigan. Within a few months, he became the assistant librarian at his alma mater and later, went to teach at Dennison University. While Kelley had the opportunity to pursue a teaching profession, he could not shrug off his ministry call. In September 1868, he began his biblical studies at the Theological Institution at Newton, Massachusetts. To pay for his seminary studies, he took on the task of tutoring students and worked in local churches. He was able to prepare a sketch of Mr Thomas (a missionary in Burma). He took the opportunity to meet and consult with the esteemed missionary, Abram Taylor Rose, who had recently returned from Burma.

On April 26, 1869, Kelley wrote to his parents: "I think I am now entirely and thoroughly convinced that it is not my duty to be a teacher in this country, but that I can best serve God by going to the dark places of the earth to proclaim the Gospel. Pray for me, all of you, that I may be guided aright: that God may direct me in the way in which I can best serve him."

During his studies, the call to missions did not fade. On December 27, 1870, Kelley and classmate Sabin Tillotson Goodell presented their cases to become missionaries for the ABMU. Kelley's teaching gifts were abundantly clear, and many suggested he take on general education work in Burma. While gifted for this, he felt called to preaching the Gospel among the Shan. He was eventually given this mission task as his gifts in languages would help with the translation of a Shan bible.

In June 1871, Kelley and his friend and classmate Sabin Goodell graduated from Newton Theological Institution. The next day he married Jennie V. Blackadar. They went and spent time with his family and began to make preparations for their move to Burma. They also met the Reverend and Mrs Moses Holman Bixby, who described their work among the Shan.

In October 1871, the Kelleys were commissioned by the ABMU by veteran missionary Reverend D. L. Brayton of the Pwo Mission in Burma. On October 21, 1871, a party of seven missionaries, including Edwin and Jennie Kelley (Shan Mission), Mr and Mrs Hopkinson (Karen Mission), Mr and Mrs Keith (Assam Mission) and Mrs Danforth (Assam Mission) departed Boston. Arriving in England after a rough journey, Jennie Kelley needed more time in London to recuperate from sickness. After improving, the Kelleys departed and made their way to Burma, stopping in Madras and Arakan along the way. On January 31, 1872, the Kelleys arrived in Rangoon (now Yangon) and were welcomed by Dr Stevens, Reverend Bennett and Reverend Vinton, and stayed in Reverend Colburn's house. A week later, they departed by boat upriver for Toungoo and arrived on February 20, 1872. There they met ABMU missionaries Josiah and Ellen Cushing (Shan Mission), Alonzo and Louisa Bunker and and Dr Francis Mason (Karen Mission), and Benjamin and Susane Cross (Burma Mission). Soon after, the Kelleys travelled up to the mountain top of Taungyi to commence their Shan language studies. While there, they faced the loss of their newborn daughter in May 1872.

When the Kelleys arrived, they found 13 members in the Toungoo church (eight Shan and five Burmese). These members had come to Christ through the work of Moses Bixby and Josiah Cushing. One of them was a widowed Shan woman named Mai. She had left Shan State to go on a pilgrimage of merit to see Shwedagon Temple in Rangoon. Along the way, she stopped in Toungoo, where she met some Christians. After hearing the Gospel, she wanted to learn more and went to study under Moses Bixby. She soon became a disciple of Jesus Christ.

While working on his Shan language studies, Edwin Kelley oversaw the Shan school of 25 students. The school was mainly a primary school to help older Shan students learn how to read and write. It had an evangelistic goal to share the Gospel with the students who came to study there. While Kelley took charge of the Shan school, he confessed that the main work was accomplished by Toon La, the head Shan teacher. However, Kelley also showed a remarkable propensity for picking up the language. Within six months of his arrival, he took up the task to preach in Shan. His evangelism gifts shone through and soon, two of the students at the school, Sang Sou and Ing Tah, shared their desire to become disciples of Christ. Kelley baptised these two men on September 1, 1872.

Kelley received a great deal of favour from the ABMU missionaries who found him a humble companion and excellent scholar. Josiah Cushing was especially pleased to have a fellow worker who could assist him in helping with the task of translating the Shan bible.

The following month, the missionaries in Toungoo went to the annual ABMU meeting in Rangoon. After the meeting, Cushing, Kelley and many evangelists and Shan Christians set off on a tour into Shan State. Cushing wrote of Kelley, describing his work: "During our trip to the Shan States he was constantly talking to the Shans and distributing tracts, sometimes in the zayats and sometimes in the bazaars, repeatedly saying that he had never supposed that he could preach so much to the people in such a journey.”

On January 1, 1873, the team arrived along Lake Nong Saweet. Kelley was able to shoot a waterfowl and swam out to retrieve the bird. As Kelley swam out, the new Shan convert, Ing Tah, helped dry out Kelley's wet clothes. He then caught a glimpse of Kelley in the middle of the lake, lying on his back with his arms stretched up to heaven. Seeing this as odd, Ing Tah called and then swam out to help, but Kelley sank. Ing Tah was unable to reach him in time. The rest of the team soon arrived on the scene and did their utmost in saving Kelley. Unfortunately, the effort took four hours, and they finally recovered Kelley's lifeless body. 

On the same day, a grave was prepared under a Mai Song tree on the northern brow of a hill as it slopes toward the southern edge of Lake Nong Saweet. Edwin Kelley's body rests there to this day, in the land he was called to, where it now awaits the final resurrection in Christ. Five months later, Jennie Kelley gave birth to another child, who sadly lived for just a few weeks. She returned to the United States and died in 1889.