In 1847, Collins was called to New York, where he was ordained an elder and commissioned along with M. C. White and his wife to China. They sailed from Boston on April 15 and reached Foochow on September 6. To start an opening for the missionary work, Collins set up a school for boys in 1847 and another in 1848. He also worked with M. C. White on Bible translation and distribution of tracts. In 1850, he was appointed superintendent of the Foochow Mission.
Collins' short tenure in China was fraught with impediments and obstacles, including the strong Chinese xenophobia, the formidable language barrier, the poor sanitation and bad living conditions, and finally an illness that compelled him to return home to Michigan in 1851. He never regained his health afterwards, and at just 29 years of age, he died at his parents' home at Gregory, Lyndon Township, Washtenaw County, Michigan, where he is buried, May 1852, leaving no children.