Ezequiel was struck by malaria, which forced him to leave the island. When he was able to recover from the disease, he was again made in charge of a mission in Calapan. Though only 28 years old, both the Archbishop of Manila and his Recollect Prior assigned him as Vicar Forane of Mindoro. In 1876, he was transferred to what is now Las Piñas and worked zealously for the development of the lives of the people in the area. The town suffered many major calamities during his pastorship, yet the people did not lose hope because of his example. This saintly way of life that he exemplified caused the people of Las Piñas to oppose his transfer to Santo Tomás, Batangas. The appeal, as strong as it was, was not successful and St. Ezequiel was transferred to Santo Tomás. However, he was recalled to Manila because he was appointed General Preacher of the Order of Augustinian Recollects. The people of Santo Tomas also made an appeal to suspend the order but like what happened in Las Piñas, their request was not granted. He assumed the post in October 1880 and as Preacher General, was assigned parish priest of Santa Cruz Church, assuming the post in February 1881. A year later, he was assigned to take charge of the Recollect hacienda in the towns of Imus and Bacoor in Cavite. During his stay, the towns were struck by cholera and the priest worked hard to administer the Last Rites to as many of the faithful as possible that of the 3,200 victims, only three died without receiving the Last Rites. His saintly life made him elected as Superior to the Seminary in Monteagudo in 1885. Through this post, St. Ezequiel imparted his missionary zeal to many missionaries to the Americas and the Philippines. It was in 1888 that he once more crossed the Atlantic Ocean and became the head of the Recollect mission in Colombia. He served as Vicar apostolic of Casanare and was named bishop of Pinara, Colombia on October 23, 1893. He became Bishop of Pasto, Colombia on December 2, 1893. He was noted for his generous charity to the faithful of his diocese and his ardent attacks against the liberal party from the pulpit. As most of the Colombian Church hierarchy, Ezequiel Moreno aligned himself with the Colombian Conservative Party. During the Thousand Days War, he used his writings and preaching sermons to attack the Colombian Liberal Party and to urge Catholics to fight the liberals and to "defend their religion with Remingtons and machetes", promising automatic Absolution.