In this study, we identified and analyzed characteristics of top-cited single-author articles published in the Science Citation Index Expanded from 1991 to 2010. A top-cited single-author article was defined as an article that had been cited at least 1000 times from the time of its publication to 2012. Results showed that 1760 top-cited single-author articles were published in 539 journals listed in 130 Web of Science categories between 1901 and 2010. The top productive journal was Science and the most productive category was multidisciplinary physics. Most of the articles were not published in high-impact journals. Harvard University led all other institutions in publishing top-cited single-author articles. Nobel Prize winners contributed 7.0% of articles. In total, 72 Nobel Prize winners published 124 single-author articles. Single-authored papers published in different periods exhibited different patterns of citation trends. However, top-cited articles consistently showed repetitive peaks regardless of the time period of publication. “Theory (or theories)” was the most frequently appeared title word of all time. Leading title words varied at different time periods, and only five title words, method(s), protein(s), structure(s), molecular, and quantum consistently remained in the top 20 in different time periods.