Inness began his artistic career painting in the style of the Hudson River School artists. However, during trips to Paris in the early 1850s, Inness came under the influence of artists working in the Barbizon school of France. Barbizon landscapes were noted for their looser brushwork, darker palette, and emphasis on mood. Inness quickly became the leading American exponent of Barbizon-style painting, which he developed into a highly personal style. He became regarded as the finest American landscape artist of his time.

Inness was the 5th of 13 children of a grocer. His family moved to Newark, New Jersey when he was about 4 years of age. In his teens, Inness worked as a map engraver while sketching scenes from nature on the side. During this time period, he attracted the attention of fellow artist Regis Gignoux, whom he soon after moved to New York City to study with. When Inness was in his early 20s, a patron named Ogden Haggerty sponsored a trip the artist took to Europe to paint and study. Inness spent a year in Italy as well as a year in France before returning to the United States.

During the 1850's, Inness was commissioned by the Delaware, Lackawanna and Western Railroad to create paintings which doucumented the progress of DLWRR's growth in early Industrial America.

Innes was heavily influenced by the theology of Emanuel Swedenborg. Introduced to Swedenborgian thought by artist William Page during the 1860's, he took inspiration from Swedenborgian ideas regarding the Divine in Creation, particularly the notion that every thing in nature had a correspondential relationship with something spiritual and so received an "influx" from God in order to continually exist.

Innes was also influenced by William James (who was also influenced by Swedenborg). In particular, Innes was inspired by James' idea of consciousness as a "stream of thought", and also his ideas concerning how mystical experience shapes one's perspective toward nature.