Black garlic is produced through thermal processing and is used as a healthy food throughout the world. Compared with fresh garlic, there are obvious changes in the color, taste, and biological functions of black garlic. To analyze and explain these changes, the contents of water-soluble sugars, fructan, and the key intermediate compounds (Heyns and Amadori) of the Maillard reaction in fresh raw garlic and black garlic were investigated, which were important to control and to evaluate the quality of black garlic. The results showed that the fructan contents in the black garlics were decreased by more than 84.6% compared with the fresh raw garlics, which translated into changes in the fructose and glucose contents. The water-soluble sugar content was drastically increased by values ranging from 187.79% to 790.96%. Therefore, the taste of the black garlic became very sweet. The sucrose content in black garlic was almost equivalent to fresh garlic. The Amadori and Heyns compounds were analyzed by HPLC-MS/MS in multiple reaction monitoring mode using the different characteristic fragment ions of Heyns and Amadori compounds. The total content of the 3 main Amadori and 3 Heyns compounds in black garlic ranged from 762.53 to 280.56 μg/g, which was 40 to 100-fold higher than the values in fresh raw garlic. This result was significant proof that the Maillard reaction in black garlic mainly utilized fructose and glucose, with some amino acids.