Seymour signed with the New York Giants of the National League (NL) during the 1896 season, making his Major League Baseball (MLB) debut on April 22. A sometimes wild pitcher, "The New York Times" described him as having a "$10,000 arm and a $00,000 head". Seymour set an MLB record with three errors in one inning, a record later tied by Tommy John. However, he pitched to an 18–14 win–loss record in 1897, with a 3.37 earned run average (ERA), while recording 149 strikeouts, good for second in the NL.