The objective of this work was to obtain degradation kinetic models of riboflavin and ascorbic acid, and to evaluate the potential of front-face fluorescence (FFF) spectroscopy to predict their concentration in milk after thermal processing. A factorial design with three temperatures (70, 80 and 90 °C) and nine times (from 0 to 60 min) of heat treatment was used. Degradation kinetics of both vitamins were of first order. Predictive kinetic models using the Arrhenius equation had a variability coefficient of 2.26 and 3.64% for riboflavin and ascorbic acid, respectively. With fluorescent predictors such as tryptophan, Maillard compounds and riboflavin, prediction models with coefficients of variation smaller than 3.57% for riboflavin and ranging from 4.24 to 14.25% for ascorbic acid were obtained. In conclusion, FFF is a viable alternative to predict riboflavin and ascorbic acid content of milk which could allow in-line monitoring and control of thermal damage.