When delving into the depths of Karaisalı's history, remnants from the Roman era are encountered. The remains of the city, known as Midilli during the Roman period, are located to the south of Karaisalı.

It is estimated that Midilli, one of the major cities of its time, harbored a population of over 70,000. After being destroyed during Alexander the Great's invasion of Anatolia, the city of Midilli witnessed the presence of many civilizations. However, the imprint of Turkish civilization, stamped upon the region following the arrival of the Turks in Anatolia, is highly discernible, with numerous Seljuk and Ottoman artifacts and names being found to this day.

With the settlement of Seljuk Turks in the region, we see that the city's name was changed to Chechenli. We know that the present-day district's population is descended from the Ramazanoğlu and Menemencioğlu lineages originating from the Yüreğir Plain. The current name of the district is attributed to Kara İsa Bey from the Ramazanoğlu family.

When we open the pages of historical documents available to us, we find political turmoil in Anatolia, the Seljuk state falling under Mongol rule. The gathering of hundreds of thousands of Turkmen nomads from Antioch to Jerusalem becomes significant. With the support of the Mamluks, this population was directed towards Çukurova from Antioch starting from the 1290s. The 1340s witnessed Mamluk policies of conquest along the Ceyhan River and its shores. Armenians were defeated in battles. In the 1350s, the Üçoklu Turkmen were under the administration of Yüregir Beyoğlu Ramadan. They roamed around the Adana and Tarsus regions for a while.

Ramadan Bey established his winter camp in the area north of present-day Camili Village. Adana was captured by Ramadan Bey in 1360. However, Ramadan Bey had become the Turkmen Emin ruler of the Adana Region with the approval of the Egyptian Sultan in 1352. Ramadan Bey's most loyal men were Kusun, Kara İsa, Özer, Gündüz, and Kuştemür. Kara İsa Bey was given Midilli town as a winter campsite and Kızıldağ and its surroundings as a summer pasture. However, it is understood that Karaisalı seized the Annahşa castle through a fierce struggle or battle. The Annahşa castle was the central point of Kara İsa Bey's conquest territory.

Kara İsa's son, Hamza Bey, arrived in Cairo in 1427 and pledged allegiance to the Mamluk Sultan. Alongside Karaisalı Bey, there were also the Dündarlı, Hacılı, and Bulgarlı tribes. In 1530, Kara İsa's son, Sevindik Bey, was at the head of the tribe.

The registers of Sultan Suleiman the Magnificent show that there was a special interest in Karaisalı. Ottoman archive documents reveal that in the registers of land ownership and taxation (Tapu-Tahrir) of the Adana province from the 1520s, 30s, 40s, and 50s, Karaisalı's social and economic situation is detailed. Let's take a look at archive document number 998. In Karaisalı, which was a district of Adana province, the communities and tribes living in obas (nomadic tents) are as follows:

Mustafalı, Tekehacılı, Uçar, Murculu, Köşkerli, Toraşan, Çomaklı, Köçekli, Aşıksarılı, Diğerköpekli, Aldoshacılı, Nureddin-Yapakoğlu, Çömelek, Elcik, Orkud aşık, Alibeyli, Ulu keçi, Turgudlu, Sarıçobanlı, Şeyhmehmedli, Kesik, bayramlık, Mutanlı, Babasıoğlu, Albaşlı, Oruçbeyli, Keçili, Avcıhacılı, Bektaşlı Botuklu, Yapallıoğlu, Arabhasanlı Dönarslan, Şeyhhacıhalife, Kerceoğlanları, Karaisalı, Kenger, Kaşıkcılar, Salur, Karacaisalı, Köl düğün, Uzadan, Sarıçobanlı, isakocalı, Emirilyaslı, ilenekli, Heceli, ilhanlı, Turhanlı, Kesrici, Çomaklı, Kuli, Canikler, Kızanlı, Tırnak.

Let's note that the obas listed above in Karaisalı were included in the register from 1526. In the same year, there were 73 oba communities and 1,956 households in Karaisalı, and the population of Karaisalı's central district and villages was close to 10,000. If called upon by the Sultan, 2,731 soldiers were ready for battle. In Karaisalı, in the same year, there were 162 Christian households compared to 1,834 Turkish households. That is, by the 16th century, 90% of Karaisalı was Turkish, indicating a strong Turkification movement in Karaisalı since the time of the Ramazanoğlu dynasty.

The branches of Karaisalı are also mentioned in the Ottoman Archive's 1572 detailed register of the Adana province. The tribes and their branches associated with Karaisalı among the nomads living in Karaisalı are also explained. Below is a list of the branches of Karaisalı:

İsa, Kocalı, Emirilyaslı, Çeçeli, Günece, Yardımşahlı, Abdalanoğlu, Kararnandepeli, Alhanlı, Kestel, Göçerili, Çömelek, Hatibli, Ebiga, Gerce, Şeyhmehmedli, Yayasalı, Yahyaoğlu, Köşkerli, Kırtoy, Avcıhacılı, Alibeyli, Yapallı, Yahşihanlı, Dönarslan, Bunsuz, Ulukeçi, Lala, Canikler, Karacaisalı, Umurlu, Sarıçobanlı, Bayramlı, Eğlenceli, Urunguş, Bektaşlı, Yargı, Emelcik, Balabanlı, Gümeç, Salur, Gerdekli, Arabhasanlı, Furatlı, Uzadan, Örküdşeyh, Koğaşar, Alibeyli. Karaisalı has many hamlets. We believe that the homeland of Karaisalı's Chechenli tribe is the current city center of Karaisalı.