Zeng Guofan regarded Zuo Zongtang as a brother. Zeng and Zuo were fellow townsmen in Hunan. Since the second year of Xianfeng, Zeng Guofan organized the Hunan Army in his hometown of Hunan, and he had contacts with Zuo Zongtang. At that time, Zuo Zongtang was an aide to Zhang Liangji, the governor of Hunan Province. Due to official duties, he kept exchanging letters and their friendship grew stronger. Zeng Guofan later became prominent because he led the Hunan Army to suppress the Taiping Army, overseeing two rivers and four provinces. Although Zuo Zongtang did not pass the imperial examination, he was famous all over the world for his talent and learning. In the 10th year of Xianfeng's reign, Zuo Zongtang was hired as a staff member by Zeng Guofan. Later, due to Zeng Guofan's strong recommendation, he was appointed as a fourth-rank Jingtang candidate by the Qing Dynasty and became Zeng Guofan's capable general. Zeng Guofan's trust in Zuo Zongtang could not be increased. In his correspondence, he always treated Zuo Zongtang as a brother and regarded himself as a younger brother.

Hong Xiuquan's successor was involved in a life-and-death lawsuit. However, behind the apparent friendship between the two, there were not without conflicts. Zuo Zongtang has an upright and decisive personality, and hates evil as much as hatred. Although talented, his long-term depression and dependence on others made him particularly sensitive. Once, Zeng Guofan used the word "Yang Yang" in a letter to Zuo Zongtang out of humility. Zuo Zongtang was very unhappy and said: "He wrote 'Yu Yang' and asked me to 'Lou Zuo'!" Later, word reached Zeng Guofan's ears, and a rift arose. However, the real breakdown of the relationship occurred when Tianjing City was conquered. The two filed a lawsuit with the court over whether Hong Xiuquan's successor, the young master Hong Futai, was dead.

After first capturing Tianjing, Zeng Guofan reported to the court to retaliate against Jinling. All the thugs were killed in one sweep. He also pointed out that after the city was broken, the false young master accumulated salary in the palace and set fire to himself. This highlights Zeng Guofan's complete victory over the Taiping Army. Unexpectedly, Zuo Zongtang also gave in, saying that according to the evidence of the refugees who escaped from Jinling, the pseudo-young master Hong Fuchi fled from Dongba to Guangde, and was welcomed into the capital of Huzhou by Taiping Army general Huang Wenjin. He wanted to use the name of the pseudo-young master to summon the remaining Taiping troops. . After the Qing Dynasty saw Zuo Zongtang's report, they were very dissatisfied with Zeng Guofan. Zuo Zongtang's memorial really annoyed Zeng Guofan. So Zeng Guofan retorted, implying that Zuo Zongtang was bluffing and was just asking for credit and reward. Zuo Zongtang could not give up, so he wrote tens of thousands of words to defend himself and criticized Zeng Guofan verbally and writtenly. At this point, the personal relationship between the two ended.

In his later years, Zuo Zongtang would scold Zeng Guofan when he met everyone. After Zuo Zongtang pacified Xinjiang, the Qing government planned to make Zuo Zongtang a first-class duke. The Empress Dowager Cixi believed that Zeng Guofan conquered Jinling in the past and was only granted the title of Marquis. Zuo Zongtang was recommended by Zeng Guofan; and the generals Liu Songshan and the Hunan army that Zuo Zongtang relied on for his achievements in Xinjiang were sent by Zeng Guofan. If Zuo Zongtang was granted the title of Duke, then the court would be too weak to Zeng Guofan. So Zuo Zongtang was granted the title of First Class Marquis of Ke Jingbo and Second Class Marquis of Jin, to show that he was slightly inferior to Zeng Guofan. Therefore, in his later years, Zuo Zongtang became even more dissatisfied with Zeng Guofan, so he scolded Zeng Guofan whenever he met, often chattering endlessly.

However, when Zeng Guofan passed away, people speculated that Zuo Zongtang might not pay tribute, but Zuo Zongtang sent an elegiac couplet: "Knowing people wisely and seeking the country with loyalty, I feel ashamed to be inferior to Yuan Fu; if we are of the same mind, If you attack gold, it will be as good as a stone, and your relationship will last a lifetime." This is Zuo Zongtang's sincere evaluation of Zeng Guofan and their relationship.