Henry Trost was the architect of the Manning House and submitted his drawings in 1907. It was to be built among wheat fields not too far east from the Rio Santa Cruz.

Levi Manning was a newspaperman that became a prominent businessman. He arrived in Tucson in 1884 and made the dusty town his home, as he had run out of money. The twenty-year-old was fleeing his hometown in Missouri where his involvement in a prank having something to do with circus elephants that had gone badly for his small town. Within a decade his fortunes were much brighter. He had invested in mines, the Canoa cattle ranch, an ice and electric company, a big downtown hotel, water wells in Menlo Park, fertile land in the Flowing Wells area, railroad construction projects in Mexico, oil wells in California, even a mule-powered streetcar line in Tucson, which he electrified. The North Carolina-born, Mississippi-raised son of a congressman and Civil War veteran was the grandson of plantation owners. He served as U.S. surveyor-general for the Territory of Arizona in the 1890s and was elected Tucson's 17th mayor in 1905.

Around 1890, there existed in Tucson a group of young successful bachelors. They maintained close personal ties within their business dealings which involved finance, law, real estate, cattle and mining. There was a shortage of marriageable women in their social setting and many of these men married later in life. These single gentlemen formed residential clubs, the best known was the Owls, to support their interlocking social connections and lifestyle and social connections a cut above the taverns downtown. There were three residential locations for the Owls. Levi was one of these bachelors who left the Owls to marry and bought the First Owls Club on N Main Street for his wife. Eventually Manning was a contributor to the development of the upscale area of Tucson where Owls Club and upscale homes existed, which eventually became known as “Snob Hollow”. His home was to be part of this area built over ancient alluvial flood soils near the Rio Santa Cruz. The richness of the soil lent itself for creation of attractive gardens and cultivation of semi-tropical plants.

Levi Manning’s wife, Gussie, enthusiastically provided her design ideas for their new home on Paseo Redondo, combining Spanish Colonial, Territorial, Italian Renaissance and Prairie styles for the 12,000 square foot home. The foundation was cut rock from the Sentential Peak quarry and the exterior was stucco over fired brick. Mexican-born artist, Salvador Corona was commissioned to paint frescoes in the building's south rotunda. The exotic birds and floral designs in pale blue, gold and silver remains today. The home was the first in Tucson to have a private swimming pool. There were stables and a seven-car garage and with 16 rooms, providing plenty of accommodations for servants.

The Manning family lived there for 28 years. After Levi’s death in 1935, six owners have held title to the Manning House. Clare Schnaufer lived there until her marriage in 1948, when she was expected by the family to move to her husband’s home. Clare was adopted at age 3 by Levi’s son Howell Manning Sr. Clare happily retired to a 20-acre ranch after leaving the Manning House as it's last resident.

The house was sold by the Mannings. They had a home in Guaymas, Sonora, as well as Canoa Ranch, which at its peak covered 100,000 acres south of Green Valley. The Manning family empire started to dissolve after Howell Jr. was killed in a car accident in 1951. Howell Sr. gradually sold off much of the ranchland before he died in 1966.

The Manning house fell into disrepair for 30 years starting in the 1950’s. The Elks Club added 20,000 square feet of additions and sold the property to the city in 1979. This is when the original building was added the National Registry of Historic Places. A Canadian developer spent $1.5 million to convert the house to office space in 1984. Colleen Concannon made $3 million dollars of renovations after she bought the property in 1997 and until 2013 it was managed as a events center. Facing near foreclosure by Collen’s bank, El Rio Community Health finally purchased the building for their administrative offices and therefore rescued a historic 35,000 square foot property on 5.2 acres that could have easily been demolished by many local politicians that valued the land over its historic value.