Late blight disease (LBD) caused by the pathogen Phytophthora infestans (PI) is the most devastating disease limiting potato (Solanum tuberosum) production globally. To better understand the molecular responses of different potato cultivars to LBD, we investigated the proteomes of three potato cultivars namely Favorita Faudio (FA), Mira (MA), and E-malingshu N0.14 (E14) infected with PI. Tandem mass tags (TMT) quantitative proteomics was used to reveal the proteome dynamics in the three cultivars one week after inoculation. A total of 3306 proteins was identified in FA, MA, and E14, together 2044 proteins were differentially expressed (DEPs), in which MA and E14 hierarchically clustered together separate from FA. Comparison of protein expression patterns, functional category and pathway enrichment tests highlighted significant differences and similarities between the three cultivars in terms of defense mechanism against PI.