Indiana's sixth governor, David Wallace was born in Mifflin County, Pennsylvania, the first child of Andrew, a surveyor, newspaper publisher, and tavern owner, and Eleanor (Jones) Wallace, niece of Revolutionary War naval hero John Paul Jones. In 1807, the Wallace family moved to Miami County, Ohio, where Andrew worked as a surveyor and served as the county's first treasurer. During the War of 1812, he was quartermaster to General William Henry Harrison and struck up a friendship with the future president. After the war, Andrew moved to Cincinnati and was part owner of the Liberty Hall newspaper.

Through his friendship with Harrison, Andrew Wallace obtained an appointment for his son David to the United States Military Academy at West Point. Shortly after David enrolled at West Point in 1817, the Wallace family moved to Brookville, Indiana, where Andrew ran a tavern. After graduating from West Point in 1821, David served as an instructor in mathematics at the institution. Resigning his commission on 1 June 1822 he rejoined his family in Brookville and began the study of law with Judge Miles C. Eggleston. Admitted to the bar in 1824, Wallace established a practice in Brookville, where he also served in the local militia company, rising to the rank of colonel. On 10 November 1824 he married Esther French Test, daughter of judge and congressman John Test. The couple had four sons, William, Lewis (known as Lew), John, and Edward.

Reminiscing about his father in his autobiography, Lew Wallace, Civil War general, diplomat, and author of Ben-Hur, noted that David Wallace was "a man of noble presence in the slender elegance of youth, straight and tall, with a well-shaped head set squarely on his shoulders." A follower of Henry Clay and known for his skill as an orator, David Wallace began his career in Indiana politics as a Whig representative to the Indiana General Assembly, serving three terms and receiving two dollars a day in pay. In 1831 he was elected as the state's lieutenant governor, winning reelection three years later. Moving his family to Covington (located near the Illinois border), Indiana, in the spring of 1832 Wallace lost one of his sons, John, to scarlet fever. Although also stricken with the illness, Lew Wallace survived. During his campaign for a second term as lieutenant governor, Wallace suffered a severe blow when his wife Esther died of consumption on 14 July 1834. As lieutenant governor Wallace was a strong supporter of the Mammoth Internal Improvements Bill of 1836, signed into law by Governor Noah Noble, which allowed the state to borrow millions of dollars to fund the construction of canals, railroads, and roadways.

Selected by the Whig party to succeed Noble in office, Wallace defeated his main opponent, John Dumont, a fellow Whig, by approximately nine thousand votes and took office as governor in 1837. Taking over his duties as the nineteenth state's chief executive, Wallace moved to Indianapolis with his family, which included a new wife, Zerelda Sanders, daughter of an Indianapolis doctor and sister-in-law of the inventor of the Gatling gun. Zerelda Wallace later served as the first president of the Women's Christian Temperance Union, which organized in Indianapolis in 1874. The couple had two daughters, Mary and Agnes, and a son, David, Jr.

During his first year in office Wallace approved plans for the swift removal of the last Native Americans, approximately 800 Potawatomi, from the state. As governor Wallace also continued to push for internal improvements, but the financial panic of 1839 and the depression that followed abruptly halted work on the various projects and plunged Indiana into insolvency. Rejected by his own party, Wallace was not renominated for governor in 1840. A year later, however, he won election to Congress, where he served on the House Ways and Means Committee. While on that committee, Wallace cast the deciding vote in favor of a $30,000 appropriation to aid Samuel F. B. Morse's work on the telegraph. In his 1843 reelection campaign, Wallace was defeated by his Democratic opponent, William J. Brown, a former Indiana secretary of state, who castigated Wallace for allowing federal funds to support such a foolhardy venture as Morse's invention.

After his defeat, Wallace returned to the practice of law in Indianapolis. He continued to be involved in civic and state affairs; in 1850 Wallace was selected to represent Marion County in the 1850 Indiana Constitutional Convention and in 1856 Marion County voters elected him judge of the court of common pleas. He was eventually vindicated for his support of the telegraph. In 1858, when Indianapolis organized a huge celebration to mark the successful laying of the Atlantic cable, Wallace gave the main address.

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