Bliss was saved as a 12-year-old boy during a revival near his home in Pennsylvania. After working on a farm as a boy, he became a schoolteacher. He loved to sing, but had received no formal training. His grandmother paid the $30.00 tuition for him to attend the Normal Academy of Music, where his talents were sharpened.

Bliss and his wife, Lucy, moved to Chicago, where his singing soon brought him to the attention of D. L. Moody. Moody encouraged him to give up secular work for a full-time ministry of gospel music. After much hesitation, Bliss agreed that this was God's plan for his life. Together with Major Daniel Whittle, he preached and sang across the country for the next three years. Their first meeting together in Waukegan, Illinois saw a great number of converts, and they scheduled meetings around the country for revivals. One of their greatest meetings was held in Louisville, Kentucky. It was at this meeting that a young pastor named A. B. Simpson was challenged to claim the power of God on his life.

On December 29, 1876, Bliss and his wife were taking the Pacific Express from New York to Chicago. In a blinding snowstorm, the train crossed a bridge near Ashtabula, Ohio. The engine crossed successfully, but the bridge gave way and collapsed, dragging the passenger cars into the ravine below. Along with nearly 100 others, Bliss and his wife were killed.

More than 12,000 people attended the memorial service held for him in Chicago. Among the more than 80 songs Bliss wrote were: "Almost Persuaded," "Dare to Be a Daniel," "Hallelujah, 'Tis Done!" "Hold the Fort," "I Will Sing of My Redeemer," "Let the Lower Lights Be Burning," "Once for All," and "Wonderful Words of Life."