Mendeleev was born in the village of Verkhnie Aremzyani, near Tobolsk in Siberia, to Ivan Pavlovich Mendeleev (1783–1847) and Maria Dmitrievna Mendeleeva (née Kornilieva) (1793–1850). His paternal grandfather Pavel Maximovich Sokolov was a Russian Orthodox priest from the Tver region. Ivan, along with his brothers and sisters, obtained new family names while attending the theological seminary. He worked as a school principal and a teacher of fine arts, politics and philosophy at the Tambov and Saratov gymnasiums.
Maria Kornilieva came from a well-known dynasty of Tobolsk merchants, founders of the first Siberian printing house who traced their ancestry to Yakov Korniliev, a 17th-century posad man turned a wealthy merchant. In 1889 a local librarian published an article in the Tobolsk newspaper where he claimed that Yakov was a baptized Teleut, an ethnic minority known as "white Kalmyks" at the time. Since no sources were provided and no documented facts of Yakov's life were ever revealed, biographers generally dismiss it as a myth. In 1908, shortly after Mendeleev's death, one of his nieces published Family Chronicles. Memories about D. I. Mendeleev where she voiced "a family legend" about Maria's grandfather who married "a Kyrgyz or Tatar beauty whom he loved so much that when she died, he also died from grief". This, however, contradicts the documented family chronicles, and neither of those legends is supported by Mendeleev's autobiography, his daughter's or his wife's memoirs. Yet some Western scholars still refer to Mendeleev's supposed "Mongol", "Tatar", "Tartarian" or simply "Asian" ancestry as a fact.
Mendeleev was raised as an Orthodox Christian, his mother encouraging him to "patiently search divine and scientific truth." His son would later inform that he departed from the Church and embraced a form of "romanticized deism".
Mendeleev was the youngest of 17 siblings, of whom "only 14 stayed alive to be baptized" according to Mendeleev's brother Pavel, meaning the others died soon after their birth. The exact number of Mendeleev's siblings differs among sources and is still a matter of some historical dispute. Unfortunately for the family's financial well being, his father became blind and lost his teaching position. His mother was forced to work and she restarted her family's abandoned glass factory. At the age of 13, after the passing of his father and the destruction of his mother's factory by fire, Mendeleev attended the Gymnasium in Tobolsk.
In 1849, his mother took Mendeleev across Russia from Siberia to Moscow with the aim of getting Mendeleev a higher education. The university in Moscow did not accept him. The mother and son continued to Saint Petersburg to the father’s alma mater. The now poor Mendeleev family relocated to Saint Petersburg, where he entered the Main Pedagogical Institute in 1850. After graduation, he contracted tuberculosis, causing him to move to the Crimean Peninsula on the northern coast of the Black Sea in 1855. While there, he became a science master of the Simferopol gymnasium №1. In 1857, he returned to Saint Petersburg with fully restored health.