Originally, what now forms Quezon was divided among the provinces of Batangas, Laguna, and Nueva Ecija. The area was first explored by Juan de Salcedo in 1571-1572, during his expedition from Laguna to Camarines provinces.

       In 1591, the province was created and called Kaliraya or Kalilayan, after the capital town which later became Unisan. In about the middle of the 18th century, the capital was transferred to the town of Tayabas, from which the province got its new name.

       Depredation and plunder by the Moros were rampant during the Spanish regime, because they opposed the colonizers, especially in their efforts to spread Christianity. The destruction of Kalilayan in 1604 by a big fleet of moro pirates caused the inhabitants to transfer to Palsabangon (Pagbilao).

       However, even the colonized people grew discontented with the Spaniards over the centuries. The most important event in the history of the province was the Confradia Revolt in 1841, which was led by the famous Lucbano, Apolinario dela Cruz, popularly known as Hermano Pule. The province, under Gen. Miguel Malvar, was also among the earliest to join the Philippine Revolution. The Revolutionary Government took control over the province on August 15, 1898.

       The Americans then came and annexed the Philippines. A civil government was established in the province on March 2, 1901, with Lucena as its capital.

       Japanese occupation of the province during World War II began on December 23, 1941, when the Japanese Imperial Army landed in Atimonan. The occupation witnessed the brutal murders of prominent sons of Tayabas. April 4, 1945 was the day the province was liberated as the combined Filipino and American army forces reached Lucena. On 1945, the liberation on the province of Tayabas was the combined U.S. & Philippine Commonwealth ground troops including the local recognized guerrillas was invaded the Japanese forces at the end of World War II.

       After the war, on September 7, 1946, Republic Act No. 14 changed the name Tayabas to Quezon, in honor of Manuel L. Quezon, the Commonwealth president who hailed from Baler, which was one of the province's towns.

       In 1951, the northern part of Quezon was made into the sub-province of Aurora (which included Baler). Aurora was the name of the president's wife, Aurora Quezon. In 1979, Aurora was separated from Quezon as an independent province.