John Thompson III's first notable win with the team took place on January 21, 2006, in the 16th game of the season when unranked Georgetown upset No.

He led the team in scoring at 16th-ranked West Virginia with 17 points, also tying his season high with nine rebounds during the game.

In a double-overtime win at Notre Dame, he played a career-high 46 minutes, during which he scored 12 points and had seven rebounds and six assists.

He shot a season-high 8-for-12 (66.7%) from the free-throw and led the team in scoring with 18 points in the victory over Syracuse, also collecting seven rebounds and making four assists.

Against Stetson two weeks later, he saw a 25-for-25 free-throw shooting streak end, but he also had his second double-double of the season with 17 points and 10 rebounds.

As the Big East season started at the beginning of 2006, he had his fourth double-double, scoring 16 points and pulling down 10 rebounds against Providence.

At DePaul, he shot 7-for-9 (77.8%) from the field, scored 17 points and led the team with eight rebounds, and in a win over St. John's he put in a 14-point, eight-rebound performance.

He had perhaps the best game of his career in the upset of Duke, playing excellent defense, shooting 8-for-12 (66.7%) from the field, scoring 23 points, grabbing seven rebounds, and blocking three shots.

Bowman faltered over the remainder of the regular season, although he did have a double-double against ninth-ranked West Virginia with 15 points and 11 rebounds.

Early in the season in the win at Oregon, he shot 8-for-10 (80.0%) from the field, mostly from long range, and scored a career-high 25 points.

At Texas-El Paso, he shot 5-for-5 from three-point range and scored 21 points as Georgetown beat the Miners on their home court to win the Sun Bowl Tournament.

[9] The Hoyas won the Sun Bowl Tournament in late December 2005 and started the season 10–2, with one of their losses coming on the road against No.

[10] The George Washington students arrived at Georgetown to find the campus virtually deserted because of the Georgetown-Syracuse game, then underway at the Verizon Center across town.

[10] Seeded fifth in the 2006 Big East tournament, Georgetown defeated 12th-seeded Notre Dame in the first round, with Bowman recovering from his late-season slump to score 25 points,[6] Wallace putting in an eight-point, six-rebound, four-assist performance,[5] and Green scoring 13 points and pulling down nine rebounds.

[4] In the quarterfinals, Green led the team with 16 points, nine rebounds, and five assists[3] and Bowman scored 11[6] as the Hoyas upset fourth-seeded Marquette.

Wallace had 10 points and tied his season high with six assists,[5] Green also scored 10 points and had seven rebounds,[3] and Hibbert had a nine-point, 13-rebound performance,[4] but Ashanti Cook lost the ball twice in the final seconds of a close game and Syracuse prevailed 58–57 to knock the Hoyas out of the tournament.

Hibbert led the team with 17 points and nine rebounds and Ashanti Cook hit crucial free throws as Georgetown won.

Green put in a 15-point, six-rebound, four-assist effort,[3] Hibbert scored 10 points, grabbed seven rebounds, and blocked three shots,[4] and Owens played a tough defense[8] in the losing effort, and Florida was not able to secure the win until Owens missed a key three-pointer late in the game.

In October 2006, just before the following season began, sophomore guard Josh Thornton opted to leave the team, and he transferred from Georgetown to Towson at the end of the fall 2006 semester.