東吳大學創辦初期之二十六年，歷經三位美籍校長孫樂文（David L. Anderson）、葛賚恩（John W. Cline）及文乃史（W. B. Nance）。這個時期的辦學經費主要來自於捐款及學費。校園內的教學大樓林堂、孫堂及葛堂及教職學生宿舍等設施陸續興建完成，校園規模日趨完整。學科發展包括文、理、醫學、神學及法科（在上海崑山路），另有四所附中、二十所附小、惠寒小學、吳語學校等組成完整的東吳教育體系。各學科除在學術研究上表現突出，更為社會培養無數專業人才。學校以「Unto a Full-grown Man」為校訓強調學生人格的陶冶。五四運動期間，東吳學生籌組學生會，一般的學生社團則以學術研究、辯論及體育活動為主。東吳大學早期在三位校長的努力下，為日後校務發展奠定良好的基礎。
In its first 26 years, Soochow University had three American national university presidents, David L. Anderson, John W. Cline and W. B. Nance. On the campus, several buildings, the Lin Hall, the Sun Hall and the Ge Hall, and others for faculty and student accommodations were constructed. The courses provided by the university were in the fields of the humanities (liberal arts), science, medicine, theology, and law. In addition, four affiliated high schools and twenty affiliated primary schools, and then the Huihan Primary School and the Wu Yu Institute, were also part of the educational system of Soochow. The school motto, “Unto a Full-Grown Man,” was chosen to stress the importance of developing the integrity of the students. Through the successive efforts of the three presidents during this period, a solid foundation was laid for further developments.