O'Bannon also had five rebounds and seven assists, and Francisco Garcia added 14 points for the Cardinals (17-3, 5-1 Conference USA), who snapped a three-game home losing streak to the Golden Eagles and won for the 11th time in 12 games.
Since a 60-58 loss to Kentucky on Dec. 18, Louisville has won 11 home games by an average of 28 points.
Marquette played without senior point guard Travis Diener, who aggravated a left ankle sprain in the Eagles' 76-66 loss to Charlotte on Saturday. The 6-foot-1 Diener, Conference USA's assist leader and second-leading scorer, had played in 114 consecutive games.
The Eagles missed the sure-handed Diener from the start, committing seven turnovers in the first 11 minutes.
Juan Palacios' 3-pointer with 9:18 left in the half gave Louisville a 21-13 lead and launched a 14-5 spurt.
O'Bannon dismantled Marquette's defense during the run, hitting two 3-pointers, driving for a dunk and feeding Palacios for a layup that made it 35-18.
Townsend hit two 3-pointers to help Marquette cut it to 43-30 by halftime.
O'Bannon scored 17 points in the first half and set a career high by hitting all five of his 3-point attempts.
He had a layup, hit a free throw and assisted on Garcia's 3-pointer in the first 4 minutes of the second half as Louisville's lead bulged to 51-32.
Two years ago in Freedom Hall, the Golden Eagles recovered from a 19-point first-half deficit to beat the Cardinals.
Not this time.
O'Bannon hit his sixth 3-pointer, and Garcia scored eight straight points during a 17-0 Louisville run. O'Bannon punctuated his career night with a steal and breakaway dunk with 5:12 left, which put Louisville up 90-46 and prompted chants of "Lar-ree! Lar-ree!" from the capacity crowd.
The overwhelmed Eagles were 5-of-24 from the field in the second half.
The Cardinals had lost six of the previous seven meetings in a series that has evolved into a bitter rivalry.
Last year, after Marquette's 81-80 win in Milwaukee, Eagles coach Tom Crean found a Louisville scouting report that contained phony quotes attributed to him.
Two years ago in Louisville, Cardinals' forward Ellis Myles sustained a season-ending knee injury late in the Eagles' 78-73 win. Myles said later he heard Crean accuse him of faking the injury.
During pregame warmups Wednesday, Crean shook hands with Myles and the two had a brief, cordial conversation.