Treavor Scales scored four touchdowns rushing to lead Harvard to a 45-31 victory against Brown in the 112th meeting between the Ivy League teams.
Harvard outscored Brown 21-14 in the volatile fourth quarter.
Colton Chapple passed for one touchdown and ran for another for the Crimson (2-0, 1-0), who opened their season with a 28-13 win over San Diego State in which Scales rushed for 173 yards and two touchdowns.
Scales rushed for 136 yards, and Chapple finished his night 30-for-40 with 351 yards passing. Seitu Smith II caught eight passes for 92 yards and a score.
Patrick Donnelly had a big day for Brown (1-1, 0-1), completing 27 of 40 passes for 336 yards and three touchdowns. Donnelly spread his completions among nine receivers.
Harvard, however, held Brown to 3-for-10 on first-down attempts and sacked Donnelly four times.
The Crimson holds an 80-30-2 advantage in the series.