Upton began the season and held the current title of being the youngest active major leaguer second to Clayton Kershaw as of July 31, 2008. Upton collected his first big hit of the 2008 major league season on April 3. In the sixth inning of a game against the Cincinnati Reds, he broke up a no-hitter in the major league debut of Johnny Cueto with a home run. It was Arizona's only hit of the contest. The next night (April 4), he went 3 for 5 against the Colorado Rockies in their home opener with his second home run of the season. For the third consecutive ballgame on April 5, Upton homered while collecting three hits in a 7–2 Arizona victory. His third home run made him only the third player ever under the age of 21 to hit home runs in three straight games. On April 11, Upton homered off Jeff Francis of Colorado for his fourth home run of 2008 campaign. The home run was in an 8–2 victory that was the seventh straight for Arizona. The very next day (April 12), he and Arizona continued their streaks, with Upton going 3 for 3, hitting a three-run home run to dead center field at Chase Field and the Diamondbacks winning 10–3, marking their eighth straight win. Upton had a career-high four RBIs on the day.