The purpose of this systematic review was to understand Indian mothers’ milk composition and report changes in it over the past 100 years. A review was conducted in accordance with PRISMA and registered with PROSPERO (CRD42022299224). All records published between 1921 and 2021 were identified by searching databases Google Scholar, ResearchGate, PubMed, and the Cochrane Database of Systematic Reviews. All observational, interventional, or supplementation studies reporting macronutrients (protein, fat, lactose) in milk of Indian mothers, delivering term infants, were included. Publications on micronutrients, preterm, and methods were excluded. Milk was categorized into colostrum, transitional, and mature. In all, 111 records were identified, of which 34 were included in the final review. Fat ranged from 1.83 to 4.49 g/100 mL, 2.6 to 5.59 g/100 mL, and 2.77 to 4.78 g/100 mL in colostrum, transitional, and mature milk, respectively. The protein was higher in colostrum (1.54 to 8.36 g/100 mL) as compared to transitional (1.08 to 2.38 g/100 mL) and mature milk (0.87 to 2.33 g/100 mL). Lactose was lower in colostrum (4.5–6.47 g/100 mL) as compared to transitional (4.8–7.37 g/100 mL) and mature milk ranges (6.78–7.7 g/100 mL). The older studies (1950–1980) reported higher fat and protein in colostrum as compared to subsequent time points. There were variations in maternal nutritional status, diet, socioeconomic status, and regions along with study design specific differences of time or methods of milk sampling and analysis. Additionally, advancements in methods over time make it challenging to interpret time trends. The need for conducting well-designed, multicentric studies on nutrient composition of Indian mother’s milk using standardized methods of sampling and estimation for understanding the role of various associated factors cannot be undermined.