Asahel was born 1783 into a farming family in Connecticut. During his early years, he occasionally experienced religious impressions. "One evening while standing alone in a field, he watched the sun go down. The approaching night reminded him that his own life would some day fade into the darkness of the world beyond. He suddenly realized that he, like all other people, would die." These impressions were only temporary.

In the autumn of 1800 Nettleton came under powerful conviction of sin. This conviction deepened as he began to read the writings and sermons of Jonathan Edwards, but yet he remained unconverted.

It was in 1801 that a revival came to North Killingworth, and by December of that year, 32 new converts were added to the Church; by March 1802 "the congregation had been swelled by ninety-one professions." Among them was Nettleton, who, becoming "exceedingly interested" in missions societies soon had "a strong desire to become a missionary to the heathen."

Asahel operated in stark contrast to many modern evangelists. He would often move into a community for several weeks or months and study the spiritual condition of the people before attempting any revival work. His preaching was said to be largely doctrinal but always practical. Nettleton often filled the pulpits of churches where there was no pastor present. This allowed him to engage in a pastoral care for the people. This practice is typically absent in modern evangelists' ministries. He also refused to preach in any community where he had not been invited. He witnessed early in ministry the problems that can result from a pastor who feels as though he is competing with an evangelist. He also would sometimes refuse to preach in a church if he believed the request was not sincere. He rejected the idea that he was the cause of any revival and shunned those who looked to him rather than God to bring revival to their community.

Bennet Tyler and Andre Bonar wrote of the effects of revivals of which Nettleton was the instrument:

• (1) Re-established Calvinism. Calvinism seen as thoroughly evangelical.
• (2) Impact on society: revivals had a good name.
• (3) “Fruits of these revivals were permanent. They were not temporary excitements. . .”; “there were but few apostasies.”

Another historian has surmised:"Could Thomas Paine, the free-thinking pamphleteer of the American and French Revolutions, have visited [the U.S. in the final decade of Nettleton’s life],he would have been amazed to find that the nation conceived in rational liberty was “in the grip of” the power of evangelical faith. The emancipating glory of the great awakenings had made Christian liberty, Christian equality and Christian fraternity the passion of the land. The treasured gospelpassed into the hands of the baptized many. Common grace, not common sense, was the keynote of the age Religious doctrines which Paine, in his book The Age of Reason, had discarded as the “tattered vestment” of the past, became the wedding garment of many."