Humic substance (HS) is the major component of soil organic matter and chemically can be depicted as a collection of diverse, relatively low-molecular-mass components of organic molecules, forming dynamic associations and stabilized by hydrophobic interactions and hydrogen bonds on the nanometer scale. The physiological effects of HS are widely documented and summarized as a result of enhancing nutrient use efficiency, aiding assimilation of both macro and micronutrients, and stimulating plant growth by induction of carbon, nitrogen, and secondary metabolism. Based on the formation mechanism and multifunctional properties of natural HS, scientists have applied HS to extracellular electron transport, environmental repair, cellular stress, and plant growth promotion. However, due to the limited supply of natural extraction sources of HS such as lignite, weathered coal, and peat, the market supply-demand of HS is increasing year by year. Given that the molecular structures of lignin and its derivatives are similar to natural HS, it is important to ask the question of whether artificial humification methods can be used to accurately control the oxidative decomposition of large-molecular lignin and/or the radical coupling of its small-molecular derivatives to synthesize humic-like products. Another important factor to consider is whether the synthesized products can match and even surpass the effects and functions of commercial HS. This creative idea has great commercial value and application prospects for realizing a continuous increase in agricultural production and income in China. In this review, the sources, structure characteristics, and functional attributes of natural HS were briefly generalized. The latest concept, mode, and mechanism of artificial humification by the use of macromolecule lignin and its derived-small phenolics are discussed, and the differences between artificial humification products and natural HS are also compared. It is confirmed that both artificial humification products and natural HS have C, H, O, N, and S elements, but the content of N in natural HS is higher than that of artificial humification products. In addition, they both contain phenolic -OH, -COOH, and aromatic components. Compared with artificial humification products, natural HS has more aromatic structures, but fewer oxygen-containing groups. Moreover, the application values of artificial humification products in agricultural production were explored. The agronomic effects of artificial humification products are extremely significant. On the one hand, artificial humification products can ameliorate soil physicochemical properties, increase soil fertility and water-holding capacity. On the other hand, these humic-like products are also able to serve as plant nutrient pools for promoting crop growth and development, improving nutrient use efficiency and crop yield. Therefore, the practical applications of artificial humification products are of great significance for agricultural production. At present, artificial humification techniques such as chemical oxidation, hydrothermal reaction, bio-composting, Fenton reaction, and fungal laccase-catalyzed oxidation have displayed a great application potential in the precise control of humic-like substance synthesis. In particular, fungal laccase exhibits unique advantages in humic-like substance synthesis due to its dual mechanism of oxidative decomposition and radical coupling. The humification reactions induced by fungal laccase have the characteristics of high catalytic efficiency, simple and controllable operating conditions, low energy requirements, and environmental protection, thus can be used to synthesize a variety of humic-like products. Also, the advantages and disadvantages, process paths, and main control factors of these humic-like substance synthesis technologies are summarized. Hence, this study provides theoretical support and technical guidance for researchers to conquer the artificial humification of lignin and its derivatives and the technology bottleneck of its large-scale application.