Guenzburg became one of the leading spokesmen for the Vilna Haskalah, though he was a moderate who opposed radical change. He observed the practical mitzvot which, under Moses Mendelssohn's influence, he viewed as social regulations for the benefit of the Jewish community. He opposed the extremism of both the Orthodox and the secularists. When Max Lilienthal was invited to Russia by the authorities, Guenzburg joined the Vilna maskilim in attacking Lilienthal's attempts to win over the Orthodox and ridiculed his German ways and superficiality.

Guenzburg's books in the area of French and Russian history enjoyed wide circulation and helped improve his financial condition. In 1844 and 1862 he published Devir (2 vols.). Devir aroused in its readers a love for Palestine and influenced Abraham Mapu and Kalman Shullmann. His autobiography Avi'ezer, his most original work, appeared in 1864. Written in the style of Rousseau's confessions, it portrays the inner world of the Jewish child, and is a ringing attack on the heder system of education. Stylistically, Guenzburg surpasses his contemporaries by far. For the sake of accuracy he resorted to mishnaic Hebrew, introducing talmudic phrases and neologisms, many of which became commonly accepted and are still in use, for example, milhemet magen ("defensive war"), milhemet tigrah ("offensive war"), rahitim ("furniture"), beit-do'ar ("post office"), etc. Guenzburg was the literary forerunner of P. Smolenskin, J. L. Gordon, M. L. Lilienblum, and R. A. Broides. His other works include: Ittotei Rusyah Ha-Zarefatim be Rusyah (1843), on the Franco-Russian War of 1812; Pi-hahiroth (1843), a history of the wars of 1813–1815.

איגרון. עמ' VIII-VI: מכתב אל מ"ל גינצבורג, מאת אליעזר האלבערשטאם, ביאלעסטאק, 17 מערץ 1860.