In 1995, Hampton joined the Mid-Eastern Athletic Conference, commonly referred to as the MEAC after leaving the Central Intercollegiate Athletic Association. Since joining, Hampton has won dozens of MEAC titles in football, men's and women's basketball, men's and women's track, and men's and women's tennis. In March 2001, the men's basketball team made NCAA Tournament history, becoming only the fourth 15th-seeded team to defeat a 2nd-seeded team. Hampton defeated Iowa State, 58-57 on March 15, but lost to Georgetown two days later. The win still makes ESPN SportsCenter's Top 10 NCAA tournament upsets.

The Pirates won the conference in football in 1997, shared one in 1998 and 2004, and won the conference out right in 2005, 2006. From 2004 to 2007, the Pirates football team saw much success. The team won 3 MEAC Championships, 3 SBN-Black College National Championships, and was ranked in the Division I FCS top 25 poll each year. The Pirates also sent five players to the NFL Combine in 2007, the most out of any FCS subdivision school for that year. The Pirates have been dominant in tennis, winning the MEAC from 1996-1999, 2001-2003 & 2007 for the men and 1998, 2002-2004 for the women. The Pirates won the men's conference basketball tournament in 2001, 2002, and 2006.