He completed his studies at the college in Nagyszombat. He entered the order in Vienna on October 9, 1714. He completed his novitiate and his studies in philosophy in Vienna. He then taught grammar and the humanities in Gorizia for two years. He was ordained a priest in Graz in 1724, after which he went on a mission. He spent fourteen years in the missions along the Maranon River. He first worked among the Andoa Indians, and in 1732 he was entrusted with the leadership of the San Regis de Yameos reduction. In the following years, he traveled through the settlements of the Yameo Indians living in the area, which were located around the confluence of the Maranon and Ucayali rivers. He was the first European to successfully navigate the Nanay and Itatay rivers. Along the way, he created maps and provided detailed descriptions and drawings of the plants and animals found in the jungle. He learned the Yameo language and studied their way of life and customs. He established villages around the small churches he built, many of which still exist today. In addition to the Yameo, he carried out missionary work among the Omagua, Miguiano, Amaono, and Parano Indians. As a result of his successful organizational work, in 1742 he was appointed provincial superior of the Jesuit province of Quito, a position he held from 1744 to 1747.
A memorial plaque to Károly Brentán was unveiled on March 14, 2015, at St. Andrew’s Church in his hometown of Komárom.

Nagy mennyiségű kéziratot írt, amelyben feldolgozta a Maranon-vidék földrajzát, néprajzát, növény- és állatvilágát, és természetesen a missziók történetét. Az anyagot két kötetbe rendezte, és Genovába indult, hogy kinyomtassák. Útközben meghalt, a nála levő kéziratok eltűntek. Egyedül az a térkép maradt meg, amelyet könyve mellékletének szánt, ezt először Quitóban, majd Rómában adták ki.