Teplice is in North Bohemia, near the border with the German state of Saxony. It is in the valley of the Bílina river between the slopes of the Ore Mountains in the northwest and the Central Bohemian Uplands in the southeast, about 15 km (9.3 mi) west of Usti nad Labem.

According to the 1541 Annales Bohemorum by chronicler Wenceslaus Hajek, the thermal springs are fabled to have been discovered as early as 762; however, the first authentic mention of the baths occurred in the 16th century. The settlement of Trnovany was first documented in a 1057 deed, while Teplice proper was first mentioned about 1158, when Judith of Thuringia, queen consort of King Vladislaus II of Bohemia, founded a Benedictine nunnery ad aquas calidas ("at the hot springs"), the second in Bohemia. A fortified town arose around the monastery, which was destroyed in the course of the Hussite Wars after the 1426 Battle of Aussig. In the late 15th century, queen consort Joanna of Rozmital, wife of King George of Podebrady, had a castle erected on the ruins. The name "Teplice" is derived from the Old Czech, meaning "hot spring".

Teplice figures in the history of the Thirty Years' War, when it was a possession of the Protestant Bohemian noble Vilem Kinsky, who was assassinated together with Generalissimo Albrecht von Wallenstein at Cheb in 1634. The Habsburg emperor Ferdinand II thereafter enfeoffed castle and town to his general Johann von Aldringen, who nevertheless was killed in battle in the same year, and Teplice fell to his sister Anna Maria von Clary-Aldringen. Consequently, and until 1945, Teplitz Castle was the primarily seat of the princely House of Clary-Aldringen. After the Thirty Years' War, the devastated town was the destination of many German settlers.

After a blaze in 1793, large parts of the town were rebuilt in a Neoclassical style. The health resort was a popular venue for wealthy bourgeois like the poet Johann Gottfried Seume, who died on his stay in 1810, or Ludwig van Beethoven, who met here with Johann Wolfgang von Goethe in 1812; as well as for European monarchs. During the Napoleonic War of the Sixth Coalition, Teplice in August 1813 was the site where Emperor Francis I of Austria, Emperor Alexander I of Russia and King Frederick William III of Prussia first signed the triple alliance against Napoleon I of France that led to the coalition victory at the nearby Battle of Kulm.

In 1895, Teplice merged with neighbouring Lazne Šanov. Upon the dissolution of Austria-Hungary after World War I and the 1919 Treaty of Saint-Germain-en-Laye, the predominantly German-speaking population found itself in newly established Czechoslovakia. According to the 1930 census there were 30,799 people living in the city (5,232 persons of Czechoslovak ethnicity, 12 persons of Hungarian ethnicity, 23,127 persons of German ethnicity and 667 of Jewish ethnicity). Right-wing political groups like the German National Socialist Worker's Party referred to themselves as Volksdeutsche and began to urge for a unification with Germany, their efforts laid the foundation for the rise of the Sudeten German Party under Konrad Henlein after 1933. With the Sudetenland, Teplice was annexed by Nazi Germany according to the 1938 Munich Agreement and incorporated into Reichsgau Sudetenland. In 1930, 3,213 Jews lived in Teplice, 10% of the population. Under the Nazi regime they faced the Holocaust in the Sudetenland. Many fled and the Teplice Synagogue was burnt during Kristallnacht.

After World War II the Czechoslovak government enacted the Beneš decrees, whereafter the German-speaking majority of the population was expelled from Teplice. In 1945, the Princes of Clary-Aldringen, lords of Teplice since 1634, were expropriated.

In 1994, Jaroslav Kubera of the ODS became mayor of Teplice and he held the position until 2018.