Overexposure to food colorants above the allowed daily intake (ADI) level can provoke hyperactivity and other disturbed behaviors especially in children. Two new methods were developed to separate five synthetic colorants, which were Tartrazine (E102), Sunset Yellow (E110), Allura Red (E129), Carmoisine (E122), and Brilliant Blue (E133). They are labeled on a large variety of commercial food products in the Egyptian market without mentioning their definite concentrations. Therefore, there was a real need to determine these colorants with simple, accurate, and fast methods. This is the first study to determine these colorants in a wide variety of food products present in the Egyptian market. The HPLC approach with photodiode array detection was developed to quantify these colorants, on a C18 column, with a mobile phase composed of acetonitrile and water containing 1% ammonium acetate (pH 6.8), separation was carried out using a gradient program. The colorants were eluted and efficiently separated within 9 min. Then, as a complementary technique to HPLC, the UPLC-ESI–MS/MS approach was developed for identification and accurate mass measurement of the colorants found in high concentrations, the colorants were obtained simultaneously in negative mode, the run time was only 3 min. These developed methods were validated according to ICH recommendations and they were applied to analyze 65 food products including jelly powder, puddings, ice cream powders, concentrated soft drink powders, carbonated drinks, chewing gums, and sugar confectionery.