Numerical circulation modeling and observational studies have been conducted to understand the Loop Current (LC) system behaviors in the Gulf of Mexico (GoM). One of the factors that may influence the LC are upstream eddies from within the Caribbean Sea. By combining satellite altimetry, sea surface salinity and ocean color data, we demonstrate that mesoscale eddies from the western tropical Atlantic Ocean can eventually make their way to the Gulf of Mexico and likely affect the LC. In addition, our study shows that freshwater of Amazon and Orinoco River origin trapped within mesoscale eddies can also enter the GoM, potentially affecting the GoM stratification. This study provides insights into understanding variations of the LC system and showcases the roles of mesoscale eddies in connecting the open ocean and regional seas. Plain Language Summary The Loop Current (LC) is the dominant large‐scale oceanic process in the Gulf of Mexico (GoM). However, the mechanism for variations of the LC system is still unsolved. Here, we show that some mesoscale eddies originated in the tropical Atlantic Ocean can pass through the Caribbean Sea and eventually enter the GoM. These remotely generated eddies could be an important upstream factor affecting the behavior of the LC. Also, freshwater and other materials (e.g., chlorophyll) trapped in the eddies could reach the GoM as well. In addition to advancing the understanding of the LC system, this study provides an explicit example showing eddies can serve as a route connecting regional seas and the open ocean. Key Points Some eddies from the Atlantic Ocean can ultimately reach the Gulf of Mexico and likely affect the Loop Current Freshwater of Amazon and Orinoco River origin and other materials trapped in eddies could reach the Gulf of Mexico Weakening and strengthening of the long‐propagating eddies are mostly related to the variation of bathymetry