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Legal recognition of Tyler was initiated by an act of the state legislature on 11 April 1846. The Texas government created Smith County and authorized a county seat. The first plat designated a 28-block town site centered by a main square, located within a 100-acre (40 ha; 0.16 sq mi) tract acquired by Smith County on 6 February 1847. The new town was named for President John Tyler, who advocated for the annexation of Texas by the United States. A log building on the north side of the square functioned as a courthouse and public meeting hall until it was displaced by a brick courthouse in 1852. On 29 January 1850, Tyler was incorporated. Early religious and social institutions included the First Baptist church and a Methodist church, a Masonic lodge and an Odd Fellows lodge, and Tyler's first newspaper.

Though Tyler's early economy from 1847–1873 was based on agriculture, it was also well-diversified during this period. Logging was a second major industry, while complementary manufacturing included metalworking, milling wood, and leather tanning. As the seat of Smith County, the town also benefited from government activity. The local agricultural economy relied on slave labor before the Civil War.

By 1860, Tyler held over 1,000 enslaved persons, which represented 35 percent of the town's population. There was strong support for secession and the Confederacy within Tyler, as a high percentage of its residents voted for secession and many of its men joined the Confederate Army. The town was secure enough for the Confederate States of America to establish the largest ordinance plant in Texas. In 1870, the first bank in Tyler was established by Bonner and Williams. Though both the Texas and Pacific Railroad and the International Railroad (Texas) eschewed routes through Tyler, the town gained an important rail connection when the Houston and Great Northern built a branch line in 1874.

Toward the end of the nineteenth century, fruit orchards emerged as an important new business in the regional economy. Eighty percent of the county's agricultural revenue derived from cotton as it persisted as the dominant crop in the first decades of the twentieth century. Peaches were the principal fruit crop as the county fruit tree inventory surpassed one million by 1900. Disease struck the peach trees, though, and local farmers moved toward growing roses by the 1920s. Twenty years later, most of the U.S. rose supply originated in the Tyler area.

On 29 October 1895, an African American suspect named Robert Henry Hillard was burned at the stake in the Smith County Courthouse Square for the alleged murder of a nineteen-year-old white woman. Denied a trial and due process, Hillard was taken from law enforcement personnel by a white mob. Hillard's executioners were never punished. Later, two entrepreneurs combined photographs from the actual lynching with others staged with actors and sold the 16-image production as a stereographic set. One of the original sets sits in the United States Library of Congress.

On 1912, Dan Davis, an African American man suspected of attacking a sixteen-year-old white girl named Carrie Johnson, was burned at the stake in the Smith County Courthouse Square.

In 1971, the University of Texas system established the University of Texas at Tyler and Broadway Square Mall opened in 1975.

By 1980, the population grew to 70,508 and the Roman Catholic Diocese of Tyler and East Texas Islamic Society were established in the following years.

Two Tyler churches were destroyed during the 2010 East Texas church burnings. Historic preservation city planning began in 2016.

Tyler is the most populous city in Northeast Texas, and 38th in Texas. Its metropolitan area is the largest in the region, followed by the Longview metropolitan area. The Tyler metropolitan area had 230,221 residents in 2018, and the greater Tyler–Longview area had an estimated population of 371,015.

Per the American Community Survey's 2018 estimates, Tyler had a population of 105,727, an increase of 8,827 people since the 2010 census. In 2019, it increased to 106,985. There were 41,820 housing units and 35,597 households in 2018. There were 23,224 families within the city limits. The average household size was 2.84 and the average family size was 3.60. In the survey, 44.9% of households were headed by married couples living together, 16.0% had a female householder with no husband present, and 34.8% were classified as non-family households. In 2018 the owner-occupied and renter-occupied housing rate were equally 50%. The median age was 31.5 years and there were 90 males per 100 females. At the 2010 census, 96,900 people resided in the city of Tyler. The population density was 1,782.0 inhabitants per square mile (688.0/km²). The median income for the city was $42,752 and the poverty rate was 19.5%.

In 2018, the median household income for Tyler was $53,962 and the mean income was $78,886. The median value of an owner-occupied housing unit was $155,200 and the monthly payment without a mortgage was $1,317. With a mortgage, monthly owner-occupied housing costs were $515. The median gross rent from 2014-2018 was $887. About 16.7% of Tyler's population was below the poverty line in 2018.

Tyler's population has been historically predominantly non-Hispanic white as much of Texas. Its population diversified due to immigration and white flight over the 20th century.

The racial makeup of the city in 2010 was 60.5% White, 24.8% Black or African American, 0.5% Native American, 1.9% Asian, 0.03% Pacific Islander, 10.3% from other races, and 2.0% from two or more races. About 21.2% of the population were Hispanic or Latino of any race. In 2018, 49.4% of Tyler was non-Hispanic white, 24.49% Black or African American, 3.4% Asian, 0.6% American Indian or Alaska Native, 0.2% Native Hawaiian and Other Pacific Islander, 0.5% from some other race, and 2.0% from two or more races. An estimated 22.2% of the population were Hispanic or Latino of any race in 2018. The largest Hispanic or Latino group were Mexican Americans at 21,118, followed by Puerto Ricans, Cubans, and other Hispanics or Latinos. A little over 10% of Tylerites were foreign-born. The most common immigrants to the city are Mexicans, Indians, and Salvadorans.

Sperling's BestPlaces determined 73.2% of Tylerites and the surrounding area identify as religious as of 2020. As part of the Bible Belt, Protestant Christianity is the largest religious group, followed by Roman Catholic Christianity. According to the study, 31.1% of Tylerite Christians are Baptist, primarily affiliated with the Texas Baptists,Southern Baptist Convention,National Baptist Convention, USA, Inc, National Baptist Convention of America, and Full Gospel Baptist Church Fellowship. The Catholic community of Tyler and its metropolitan area are primarily served by the Roman Catholic Diocese of Tyler. Following, 6.6% of the population were Methodists, mainly affiliated with the United Methodist Church and African Methodist Episcopal Church.

Pentecostals form the fourth-largest Christian group in Tyler (5.2%) and the largest Pentecostal bodies within the area are Assemblies of God USA and the United Pentecostal Church. An estimated 1.2% are Latter-day Saints. Of the Christian population, 0.9% identified as Anglicans or Episcopalians, 0.7% Presbyterian, and 0.6% Lutheran. Roughly 13.6% of Tylerites are of another Christian faith including the Eastern Orthodox Church and Jehovah's Witnesses.

The Anglican or Episcopalian community are divided between the Episcopal Church in the United States and Anglican Church in North America. The Episcopal Church USA-affiliated Episcopal Diocese of Dallas has congregations in Tyler. The Anglican Church in North America also has congregations in Tyler and its metropolitan area. The Diocese of Mid-America is the ACNA's diocese in Tyler, consisting of one church. This diocese is also a member of the Reformed Episcopal Church.

Presbyterian and Lutheran bodies operating in the area include the Presbyterian Church (USA) and Presbyterian Church in America, and the Lutheran Church-Missouri Synod and North American Lutheran Church. The Eastern Orthodox community is served by the Orthodox Church in America's Diocese of the South.

The oldest continuously active church in Greater Tyler is the historic over 152 year old New Harmony Baptist Church, located about 10 miles outside of the city of Tyler.

St. Joseph the Worker Parish, one of the few churches in the United States dedicated to the exclusive use of the Traditional Latin Mass, is another continuously active church. It is staffed by the Priestly Fraternity of St. Peter. The city also is the home of the Cathedral of the Immaculate Conception and the Sanctuary of Our Lady of Mount Carmel, a century-old church recently^[when?] renovated and declared a historic and heritage site by the Roman Catholic Diocese of Tyler. The Saint Peter Claver Parish, located in central Tyler, is the second largest Catholic church in Tyler and was dedicated to St. Peter Claver, a Franciscan priest that assisted the black slaves in Brazil during the slave trade to South America.

Per Sperling's BestPlaces, approximately 0.1% affiliate with Judaism compared to the state average of 0.2%, and 0.4% of the area identify as Muslims. The area's Islamic community is affiliated with the East Texas Islamic Society.