Soule University, an early Methodist institution in Chappell Hill, Washington County, was an early center of Methodism in Texas; it replaced Rutersville College, and William Halsey, president at Rutersville, became Soule's first president. The Male Department of another early Methodist school, Chappell Hill Male and Female Institute, became the nucleus for this new university, which was for male students. The Texas Conference of the Methodist Church approved plans for a central university in 1854. Prominent residents on the first board of trustees, lay and clerical, included Robert Alexander, Homer S. Thrall, Gabriel Felder, and Jabez D. Giddings. Soule University had preparatory and collegiate departments. The preparatory division opened before the university received its charter from the Sixth Texas Legislature on February 2, 1856. Masons were active supporters of the new institution. Soule University was under the direction of the Texas Conference of the Methodist Church, South, which provided the major financial support, although the East Texas Conference participated in administrating and financing the institution between 1856 and 1860. The university was named for Bishop Joshua Soule, a northern Methodist bishop, who visited Texas. College courses at Soule began in September 1856. The seven academic departments included two professorships with endowments of $25,000 each. Felder sponsored a chair of ancient and modern languages. Jared Kirby endowed another for mathematics and natural philosophy. Classes were first held in the Chappell Hill Institute building. R. J. Swearingen donated ten acres for the university to build in a different section of town, probably to keep male and female students segregated. Soule's new three-story stone building, begun in September 1858, was completed in May 1861 at a cost of $40,000. In April 1861 the trustees endowed a new chair of natural sciences.
The Civil War was disastrous for Soule University, which had the best library, endowment fund, and faculty of any Texas college before the war. Ninety-five students enrolled in the first session, 1856–57, and 150 were enrolled by the outbreak of the Civil War. President Halsey returned to his home in the North in 1860, and the new president, George W. Carter, from Virginia, resigned to raise a Confederate regiment. Most Soule students enlisted in the Confederate Army before the university closed in 1861. During the war, the army used the university building as a hospital; the classrooms were badly damaged, and the library and school equipment were destroyed or lost. Although Soule University reopened in 1867, the worst yellow fever epidemic in the area's history resulted in many fatalities among Chapell Hill residents and Soule students. The January 1869 session had just twenty-six preparatory students. Enrollment failed to recover as parents from other regions of Texas refused to send their children to an area plagued by recurring epidemics and yellow fever scares. Francis Asbury Mood, the new president, could not obtain sufficient support from the board of trustees or Chapell Hill residents to pay the university's $17,000 debt because the former patrons, the plantation owners of the area, were bankrupted by emancipation. By 1871 Mood persuaded the Texas Methodist Conference to open a school in Georgetown, outside the fever belt. Mood became first president of the new institution, later called Southwestern University.
Soule continued operation until 1888 with the financial support of the local community, student tuition, and intermittent aid from the Texas Conference. By 1873 the school was debt free due to its creditor's generosity. In 1878 Soule became Soule College. The Chapell Hill area failed to recover economically from the Civil War, and the Anglo-American Methodist residents in the region were largely replaced by non-Methodist European immigrants. Attendance dropped from sixty-six students in 1886 to twenty-nine in 1887. Chappell Hill Female College used Soule's building until that institution closed. The building was eventually demolished after use as a public school. A medical department in Galveston, authorized by the trustees February 18, 1859, enrolled 143 students in classes between late 1865 and May 1871, when its successor, Galveston Medical College and Hospital, was organized due to the incapacity of Soule to support the medical program any longer. During the medical branch's existence seventy-two graduated.