Guo Hsueh-hu was born Guo Jin-huo in Dadaocheng, the then most prosperous area of Taipei in 1908. He lost his father at the age of two and was brought up solely by his widowed mother. His artistic talent was discovered by his primary-school teacher, Mr. Chen Ying-sheng, who often encouraged him and even coached him outside school hours. It was at this time that Guo Hsueh-hu started to learn the basics of Chinese and Japanese paintings.

After graduating from the primary school in 1923, enrolled at the Taipei School of Industry (today's National Taipei Institute of Technology) in the civil engineer department but later dropped out to study independently at home because the course, which prioritized mechanic drawing using hand tools, did not match his interests. In 1925, Guo began to study painting and mounting skills at Mr. Tsai Huehu-hsi's Art Studio. Mr. Tsai gave Guo Jin-huo a pseudonym Guo Hsueh-hu. This period of studying in Tsai Hueuh-hsi's art studio was the first step in Guo's artistic career. Quite remarkably, this period also saw Guo Hsueh-hu's path crossing with that of his childhood playmate, Ren Jui-yao, and they two has since formed a lifelong friendship. In 1927, the first Taiwan Arts Exhibition was held, and Guo Hsueh-hu's ink-and-wash painting Stream through Pine Ravine was selected to be part of the exhibition. Thus was begun the legend of the "Three Youths of the Taiwan Arts Exhibition" along with fellow artists Lin Yu-shan and Chen Chin. In 1928, Guo Hsueh-hu's Eastern gouache painting, The Scenery Near Yuahshan, won the special selection prize at the second Taiwan Arts Exhibition for its sophisticated brush strokes and harmonious combination of colors. Such a special honor cemented his status in the Taiwanese painting world. Nanga painting master Matsubayashi Keigetsu praised this painting as a “variation of nanga painting” and an emblematic piece of the “Hsueh-hu school”. In the subsequent years, Guo Hsueh-hu continued to be the multiple winners of the Taiwan Arts Exhibition, Taiwan-Japan Arts Exhibition and Asashi Exhibition.

Solitude (1933), which was honored with Direct Entry at the 7th Taiwan Arts Exhibition, was inspired by a trip that Guo Hsueh-hu and his friend Ren Jui-yao took together in Japan, where they were captivated by the tranquil atmosphere of the Nanzenji Temple. This trip proved to play a crucial role to the shift of Guo's art styles, as he dropped the delicate style and refined style of Togoya painting in favor of the impressionistic tradition of ink-and-wash painting. That said, it should also be noted here that although Solitude is essentially a ink landscape painting, it demonstrates significant differences from his earlier award-winner, traditional ink-and-wash Chinese landscape painting Stream through Pine Ravine in the way that the artist gave the painting Solitude a crusty texture created using the Eastern gouache painting techniques and then finished it off with ink-and-water painting techniques. This painting demonstrated Guo Hsueh-hu's commitment to stylistic innovation, as well as the open-mindedness of the TAE's Toyoga section as it was willing to accept outstanding ink paintings. However, the art style that characterized Solitude was never taken up again by any other artists after the 7th Taiwan Arts Exhibition.

Throughout his artistic career, Guo Hsueh-hu has always been active in affairs of the art community. In 1930, he joined the Chinaberry Society – a Toyoga painters' society whose founding members included Kuohara Kotou and Kinosita Seigai. In 1934, Guo Hsueh-hu formed another artists' society called the Six Ink-stone Society with five fellow artists: Yang San-lang, Lyu Tieh-chou, Tsao Chiu-pu, Chen Ching-hui. The objective of the Six Ink-stone Society was to promote Taiwan's fine arts – especially Togoya painting, Western-style painting and Chinese calligraphy – by holding workshops and panel discussions. He and fellow artist Yang San-lang were both responsible for the launching of the Taiwan Provincial Arts Exhibition in 1946. Guo Hsueh-hu emigrated first to Japan in 1964 and then to San Francisco, USA in 1978. During the Japan years, Guo created many still-life paintings of flowers in the vase, while in the years of his residence in San Francisco, he traveled extensively sketching and painting scenes. A shift in art styles can also be detected from Guo Hsueh-hu's later works, as he moved from a refined and elegant art style to one characterized by an emphasis on grandeur and expansiveness.