The NCAA Division I program competes in the Metro Atlantic Athletic Conference and the annual Franciscan Cup.

Prior to joining a conference, Siena had success in the 1950s, winning the National Catholic Invitational Tournament in 1950 and finishing the 1950–51 season ranked 18th in the AP Poll.

They won the 1989 title in the North Atlantic Conference, with a win over Boston University, famously played in front of no fans as a result of a measles outbreak.

In 1989, Siena stars Marc Brown and Steve McCoy led the school to a triumphant victory, an 80–78 win over third seeded Stanford in the NCAA Tournament.

The 1993–1994 Saints finished 25–8 making all the way to the NIT final four at Madison Square Garden defeating such teams as Georgia Tech, Tulane, Bradley, and Kansas State.

Siena's Doremus Bennerman capped his brilliant college career with a 51-point outburst against Kansas State, winning most outstanding player honors in the NIT.

Hewitt did so leading the Saints to a 66–27 record during his three years, winning the MAAC tournament championship in 1999 and taking regular season crown in 2000.

Lanier's final year saw an injury-plagued Siena team finish with a program worst 24 losses and he was fired after that season.

Siena had memorable wins over cross-town rival Albany 82–74 in overtime, as well as an 82–76 triumph at eventual MAAC champion Iona.

The Saints clinched a first round bye in the MAAC tournament with a thrilling 98–92 double overtime victory over Niagara on senior day.

On November 17 McCaffery guided Siena to a 79–67 win over #20 Stanford University in Albany, NY at the MVP Arena (formerly the Times Union Center).

Quality wins from the Saints came in the opening game of the season against Boise State, who they beat by 30, an 18-point victory against Cornell (Ivy League Conference champions and a #14 seed in the 2008 NCAA tournament), and a 6-point victory against Northern Iowa (the Missouri Valley Conference Champions and a #12 seed) in the ESPN Bracketbusters game that wasn't as close as the score indicated.

Siena would go on to lose to the #1 seeded Louisville Cardinals in the second round 79–72 after taking a four-point lead with under 7 minutes left.

Siena defeated Fairfield 72–65 in the MAAC championship game in a heart-stopping finish in overtime after trailing by 13 points early in the second half.

Alex Franklin was named MAAC tournament MVP in addition to winning the conference's player of the year award.

Siena's late rally came up short against fourth seeded Purdue in a 72–64 loss in the first round of the NCAA tournament.

Siena had solid wins over MAAC regular champion and NCAA tournament participant Iona (rallying from 20–2 down), Manhattan, Fairfield, Princeton and UAlbany.

In his first year, Patsos guided the Saints to a 20–18 record (11–9 in MAAC conference play) and the program's first-ever postseason championship, winning the 2014 CBI tournament two games to one over Fresno State.

The home portion of the three-game series was noteworthy; both games were played at the Alumni Recreation Center on the Siena campus as the MVP Arena was being used for another event.

Although the odds were heavily in favor of Duke and Wisconsin winning these games, this announcement immediately created an enormous amount of hype around the Siena College campus and the MAAC Conference as a whole.

On November 13, 2015, Siena played Duke at Cameroon Indoor Stadium, one of the most famous arenas in all of college basketball.

The Saints had quality wins over NIT participants Hofstra, St. Bonaventure and Bucknell as well as against crosstown rival UAlbany.

On April 13, 2018, Patsos resigned after 5 years at Siena, finishing with a 77–92 overall record with the Saints and following an internal investigation regarding financial troubles and abusive conduct within the program.

They would receive the 5th seed in the MAAC Tournament and defeated unanimous preseason favorite Rider in the quarterfinals before falling to Iona in the semifinals.

[11] On March 21, 2019, Christian announced he would leave Siena for the vacant head coaching position at George Washington.

[12] On March 25, 2019, Carmen Maciariello was named the 18th head coach in Siena men's basketball history.

Siena started off the regular season 6-0 but finished 6-4 for an overall and conference record of 12-4, good enough to secure the 1 seed in the 2021 MAAC Tournament at Jim Whelan Boardwalk Hall in Atlantic City, NJ.

When the regular season started, Siena lost their first four games and 6 out of their first 8, including a loss to #23 St. Bonaventure in the Franciscan Cup.

As conference play started, the Saints picked it up and finished with a 12-8 conference record which included impressive wins over MAAC regular season champions Iona at home and a sweep of eventual MAAC Tournament champions and Elite Eight appearers St. Peters.

The day after, they fell 62-74 to Ole Miss but bounced back to beat Seton Hall 60-55 in the 3rd place game.