When he was 19, Joseph Wharton apprenticed with an accountant for two years and became proficient in business methods and bookkeeping. At 21, he partnered with his older brother Rodman to start a business manufacturing white lead. Wharton’s chemistry mentor, Martin Boye, had developed a method to refine cottonseed oil and the Wharton brothers tried but failed to develop a profitable method to extract it. In 1849 Wharton started a business manufacturing bricks using a patented machine which pressed dry clay into forms. There was substantial competition in the brick business, which was affected by cyclical business swings, and after several trips to sell bricks and the brick-making machines, Wharton found the prospects for making good profits were dim. However, from the endeavor he gained valuable experience. In 1853, Wharton joined the Pennsylvania and Lehigh Zinc Company near Bethlehem, Pennsylvania, first managing the mining operation and later the zinc oxide works. Wharton proved himself by negotiating a new charter for the works, and in the difficult financial environment of 1857–1858 he took over control of the zinc works, managing it carefully so that it turned a profit. In 1860 Wharton, after some challenging negotiations with the directors of the company, developed for Lehigh Zinc the first plant to manufacture metallic zinc in America. Looking into the next business cycle, he leased the plant for four years and eventually made a robust profit from the sale of metallic zinc, used in making brass, which picked up in the Civil War years.

Hoping to profit from the use of nickel in coins, Joseph Wharton in 1863 sold his interest in zinc and started the manufacture of nickel at Camden, New Jersey, taking over a nickel mine and refining works at Nickel Mines, Pennsylvania. The Camden plant was located on the east side of 10th Street, adjacent to Cooper Creek, and had several large brick buildings and smokestacks. Wharton renamed the Camden plant the American Nickel Works, and his office there became his center of operations. However, the use of nickel in coinage was temporarily halted, and soon the Camden plant burned. Wharton rebuilt it in 1868 and made excellent profits from producing nickel because it became favored for coinage. Wharton won wide acclaim for his malleable nickel, the first in the world, and also for nickel magnets, and received the Gold Medal at the Paris Exposition of 1878. His factory produced the only nickel in the US and a significant fraction of the world supply. Eventually the surface deposits at the Gap mine were depleted and Wharton was obliged to purchase nickel ore from a mine in Sudbury, Ontario, Canada. This experience was a challenge to Wharton, who learned about market economics and protection when foreign nickel manufacturers opposed his nickel purchasing and manufacture efforts. Wharton by then had learned the value of meeting personally with his managers and regularly inspecting the mines and manufacturing plants with them. He was successful because he worked hard to increase efficiency and profitability of the businesses he acquired, and energetically pursued markets for his products. Wharton made a robust profit from his nickel business over its 40-year duration, but by 1900 its outlook was fading due to foreign competition. Wharton and a group of other United States and Canadian nickel enterprises formed the International Nickel Company (Inco) in 1902. He sold his American Nickel Works in Camden and the Gap mine for a share in the new company, and was named one of the dozen board members. By this time the profitability of his business empire did not depend on the manufacture of nickel because he had already diversified into other profitable businesses.

Joseph Wharton traveled widely and became involved in many industrial enterprises such as mines, factories and railroads. He started several enterprises on the South New Jersey property, including a menhaden fish factory that produced oil and fertilizer, a modern forestry planting operation, and cranberry and sugar beet farms. Wharton also purchased land containing ore and an iron furnace in northern New Jersey at Port Oram, New Jersey (now Wharton, New Jersey) which was located close to the Morris Canal and railroads. He purchased a coal mine in western Pennsylvania, constructing for the workers a town of 85 houses and stores along the railway. He also purchased coal land in West Virginia, iron and copper mines in Michigan, and gold mines in Arizona and Nevada. Wharton became involved in the Reading and Lehigh railroads and several others, arranging spur lines with the railroads to carry ore and finished metal products. He maintained an extensive business correspondence and in later life maintained this practice through his vacations. Wharton was a colleague of leaders such as inventors Ezra Cornell, Elias Howe and Thomas Edison, and entrepreneur Cornelius Vanderbilt. His management style evolved throughout the latter half of the 1800s, making use of new technology for communication, transportation, and production, so that he controlled many industries profitably on a larger scale than was previously possible.

Joseph Wharton was active to near the end of his life both physically and in business affairs. Until he was 72, he skated with guests on the pond at his Ontalauna estate near Philadelphia and would often go on walks with his family after dinner. Throughout his life he partook in physical exercise, total abstinence from tobacco, and restricted use of even mild alcoholic drinks. When he was nearly 80, he visited his Nevada silver mine by canoeing down the Colorado River and descending into the mine in a bucket, and when he was 81, he traveled to Germany with his grandson, Joseph Wharton Lippincott, to visit Kaiser Wilhelm II and had dinner on the kaiser’s yacht. He continued to oversee his holdings in coke manufacture in Pennsylvania and iron in northern New Jersey. He read widely in literature and was an accomplished poet. Many of his poems were inspired by trips abroad. He wrote “Stewardson’s Yarn” after an 1873 visit to Europe, “The Royal Palm” and “The ‘Sweet Reasonableness’ of a Yankee Philistine in Cuba” after a visit to Cuba to inspect mines there, and “Mexico” after an 1889 visit to the country of the same name. A domestic journey, to Nevada to see his gold mines there, resulted in “The Buttes of the Canyon”. In 1907 he was incapacitated by stroke and gradually worsened until his death in 1909.