Henry E. Huntington was born in Oneonta, New York, son of Solon Huntington and Harriett Sanders. He was educated in the public and private schools of his native city. He worked for a time in a hardware store in Oneonta, and at twenty went to New York City, where he secured employment with a large hardware firm. A year later his uncle Collis took Henry with him to inspect a part of the Chesapeake and Ohio system he was developing. Not long afterwards Henry accepted an offer his uncle made to manage a sawmill cutting railroad ties at St. Albans, West Virginia. From this time his career was fully concerned with railroads and transportation. He remained at the sawmill for five years, returned to Oneonta for a time, and then became superintendent of construction for a portion of the Chesapeake and Ohio. In 1884 he became superintendent of construction for the Kentucky Central Railroad, and two years later was named a receiver of the road. From 1887 to 1890 he served as vice-president and general manager of the road. In 1890, when Collis took over as president of the Southern Pacific, Henry was called to San Francisco, serving as assistant to the president, second vice-president, and first vice-president from 1892 to 1900.
When Collis Huntington died in 1900, he left one-third of his estate to Henry (along with a third each to Arabella and Archer). Yielding to the importunities of E. H. Harriman of the Union Pacific, they sold control of the Southern Pacific to him in 1902. For several years prior to Collis Huntington's death, Henry Huntington had become increasingly concerned with the management of electric Street railways in California, and turned his full attention to these endeavors after 1902. He had first become interested in the street railways of San Francisco, bringing about a great expansion in the system before he sold it in 1898. Turning his attention to Los Angeles, he began buying transportation lines there, and transferred his headquarters to the city in 1902. Finding inadequate local service in Los Angeles and vicinity when he entered the field, he connected, consolidated, and then extended the existing lines until, in about ten years, he had created an interurban system surpassing anything of its kind hitherto known. In addition to this "Orange Empire" as it was called, he organized the Los Angeles railway system, providing service within the city.
The interurban roads were consolidated into the Pacific Electric Railway Company, which at its peak operated over 1,200 miles of track, and about 700 route miles of service. It was the largest intercity electric railway in the United States, and represented an investment of some $200 million. Huntington shared ownership of the Pacific Electric with the Southern Pacific and Harriman until 1911 when disagreements with the latter caused him to sell the road to the Southern Pacific. He retained control, however, of the Los Angeles Railway, an 83 mile city system which used a narrow gauge 3'-6" track (as opposed to the standard gauge for the Pacific Electric). He controlled the road until his death, when it went into his estate.