Lockwood de Forest was born in New York City in 1850 to a prominent family that had made its money in South American and Caribbean shipping. He grew up in Greenwich Village and on Long Island at the family summer estate. Encouraged by his parents, Henry Grant de Forest and Julia Mary Weeks, Lockwood and his three siblings developed lifelong interests in the arts; the eldest son, Robert Weeks (1848–1931) served for seventeen years as the president of The Metropolitan Museum of Art in New York; their sister, Julia Brasher (1853–1910) wrote a book on the history of art; and their youngest brother Henry Wheeler (1855–1938) was an avid art collector and amateur landscape architect.

During a visit to Rome in 1868 nineteen-year-old de Forest first began to study art seriously, taking painting lessons from the Italian landscapist Hermann David Salomon Corrodi (1844–1905). On the same trip Lockwood met the American painter (and his maternal great-uncle by marriage) Frederic Edwin Church (1826–1900) who became his mentor. De Forest accompanied Church on sketching trips around Italy and continued this practice when they both returned to America in 1869. In 1872 de Forest took a studio at the Tenth Street Studio Building in New York.

Over the next decade de Forest experienced moderate success as a painter. He exhibited for the first time at the National Academy of Design in 1872 and made two more painting trips abroad, in 1875–76 and 1877–78, traveling to the major continental capitals but also the Middle East and North Africa.

Lockwood de Forest's nocturnes are particularly coveted by collectors for their accurate handling of moonlight. In these works, the artist's broad, confident brushstrokes are as suggestive as they are descriptive. That poetry of that which is left unsaid has to be seen in person to be fully grasped.

During his lifetime de Forest was best known as a designer. He was a strong proponent of Indian-inspired design, for which there was a fashion in the late nineteenth century. His travels fueled his interest in eastern art and architecture, and he used his knowledge to further develop his design business. His work was exhibited at the Colonial and Indian Exhibition in London in 1886 and at the World’s Columbian Exposition seven years later. De Forest’s offerings at these fairs attracted an impressive array of clients, including the industrialist Andrew Carnegie (de Forest designed Carnegie’s bedroom and library in the Andrew Carnegie House, now the Cooper-Hewitt Museum), transportation magnate Charles Tyson Yerkes, Chicago businessman Potter Palmer, and author Mark Twain.

Lockwood de Forest  traveled extensively, from Italy and Greece to the Holy Land and south into the Persian Empire and India; eventually he traveled throughout the United States, Mexico and even to China, Japan and Korea. He recorded his travels not only with design work, but with carefully rendered landscapes, which became increasingly atmospheric over the course of his career.

After beginning to winter in Santa Barbara, California around 1902 de Forest built a house and moved there permanently in 1915. He was attracted to the comfortable climate and striking coastlines of the West Coast and, while he continued to design and decorate houses, landscape painting became his primary occupation. De Forest created hundreds of oil sketches of Californian sites, and also traveled around the Pacific Northwest (1903), Maine (1905 and 1908), the Grand Canyon (1906 and 1909), Mexico (1904, 1906–7 and 1911), Massachusetts (1910) and Alaska (1912). Lockwood de Forest died in Santa Barbara in 1932.