This paper presents the obtaining and characterization of blends based on high-density polyethylene (HDPE) and plasticized starch. In addition to plasticized starch (28.8% w/w), the compositions made also contained other ingredients, such as polyethylene-graft-maleic anhydride as a compatibilizer, ethylene propylene terpolymer elastomer, cross-linking agents, and nanoclay. Plasticized starch contains 68.6% w/w potato starch, 29.4% w/w glycerin, and 2% w/w anhydrous citric acid. Blends based on HDPE and plasticized starch were made in a Brabender Plasti-Corder internal mixer at 160 °C, and plates for testing were obtained using the compression method. Thermal analyses indicate an increase in the crystallization degree of the HDPE after the addition of plasticized starch. SEM micrographs indicate that blends are compatibilized, with the plasticized starch being well dispersed as droplets in the HDPE matrix. Samples show high hardness values (62–65° ShD), good tensile strength values (14.88–17.02 N/mm2), and Charpy impact strength values (1.08–2.27 kJ/m2 on notched samples, and 7.96–20.29 kJ/m2 on unnotched samples). After 72 h of water immersion at room temperature, mixtures containing a compatibilizer had a mass variation below 1% and water absorption values below 1.7%. Upon increasing the water immersion temperature to 80 °C, the sample without the compatibilizer showed a mass reduction of −2.23%, indicating the dissolution of the plasticized starch in the water. The samples containing the compatibilizer had a mass variation of max 8.33% and a water absorption of max 5.02%. After toluene immersion for 72 h at room temperature, mass variation was below 8%.