In October 2006, the Board of Education of the Middletown Township Public School District voted on a random drug testing procedure that would require all students in extracurricular activities or with a parking space at the high school to submit their name to a pool for random selection.

[16] The Middletown High School South Eagles[5] compete in Division A North of the Shore Conference, an athletic conference comprised of public and private high schools in Monmouth County and Ocean County along the Jersey Shore.

[25][26] The 1990 team won the North II Group IV sectional title with a 15–14 win against Trenton Central High School in the championship game.

[27] In the 1995 Central Jersey Group IV final at Giants Stadium, the team defeated Piscataway High School by a score of 28–10 to finish the season with an 11–0 record.

[35] The field hockey team won the Central Jersey Group IV state sectional title in 1980, 1982 and 1995.

During Head Coach Steve Antonucci's tenure which started in 1996, the Eagles won two Central Jersey State Titles (1996 and 1999) and completed the first undefeated season in Shore Conference A-North history with a 14–0 record.

[38] The Eagles offense was the most potent in the state including the single season home run record as a team.

The Eagles were also led by All-State pitcher John Scala (10-1), and All-Shore selections Jon Klopacs (C) and Mark Fitzgerald (SS).

The 2011 baseball team won the Monmouth County Tournament and the Central Jersey, Group III title, the program's first since 1999.

[42] Softball coach Tom Erbig retired at the end of the 2016 season having led the team to 16 sectional championships and five group titles; his career record of 743-231-1 made him the winningest softball coach in the state, a title he earned in 2015 with his 722nd win, surpassing Pete Fick of Hunterdon Central Regional High School.

[43] The girls tennis team won the Group IV state championship in 1996, defeating Westfield High School in the tournament final.

[53] Three years later, during the 2007–08 season, second-year head coach Kevin Cullen led the team to the Central Jersey Group III Sectional Championship with a win over Neptune High School 45–33.

[56] The girls' basketball team won the Group III state championship in 2015, defeating Northern Valley Regional High School at Old Tappan in the final game of the tournament playoff.

[57] The team won the Group III Central Jersey state championship in 2014 with a 38–35 win against Neptune High School in the tournament final.