The purpose of the study is to examine the longitudinal trajectories of five selected South American countries in the period between 1990 and 2018, applying the Quintuple Helix Innovation Model (QHIM). The aim is to analyse the trends of each country through the relationship of its helices using indicators extracted from an international database in order to establish their articulation and synergies to go in search of sustainable development. Within this dynamic, Venezuela represents the axis country of the study and Argentina, Chile, Colombia, and Peru make up the group that allows the comparison. The research focuses attention on two periods of Venezuelan politics since they allow measuring the variations of the countries under study. The base year is 1996 and is called the pre-Hugo Chávez Frias (HCF) period; the cutoff year for the comparison is 2014 and is called the post-HCF period. The study is longitudinal and descriptive. For the analysis, the five knowledge subsystems (helices) of the QHIM were redefined in order to have precise concepts; a database was designed based on World Bank indicators that were later thematically related to each of the helices. The interrelationships between the helices of each country were also specified in order to determine which were the weakest and which had the most positive or negative influence. In order to calculate the percentage variation of the countries, the Data Envelopment Analysis (DEA) method was applied. In this sense, the most relevant finding is related to the decisions made in the last twenty years from the political helix in Venezuela because it deactivated and disarticulated the others, causing that country to collapse.