Offensive guard Quenton Nelson went to the Indianapolis Colts at No. 6, and offensive tackle Mike McGlinchey went to the San Francisco 49ers at No. 9.
This is the first time since 1993, when Rick Mirer went at No. 2 and Jerome Bettis went at No. 10, that Notre Dame had two players selected in the top 10.
Notre Dame football coach Brian Kelly reacted to the Colts' pick on Twitter.
Colts general manager Chris Ballard told reporters, "You win games up front. Y'all are gonna love him."
The Colts gave up a league-high 56 sacks last season. Asked whether quarterback Andrew Luck would like the pick, Ballard said, "I'm sure he will. I think we see now the importance of the entire offensive line, not just tackles."
Nelson told reporters: "I would say that I'm a very nasty offensive lineman. I wanna play for the best offensive line in the NFL and protect the best quarterback in the NFL."
The 49ers also put a premium on protecting quarterback Jimmy Garoppolo.
McGlinchey is expected to take over at right tackle in place of Trent Brown, then possibly transition to left tackle when Joe Staley retires.
The pick came as a surprise to McGlinchey, who did not take a pre-draft visit to the 49ers.
"I had no idea," McGlinchey said. "It's definitely a shock but I'm absolutely thrilled to be part of the San Francisco 49ers organization. It has a lot of great history with a lot of great quarterbacks and a lot of great Super Bowls."
McGlinchey is a first cousin of Atlanta Falcons quarterback Matt Ryan and said he heard about 49ers coach Kyle Shanahan from Ryan. Shanahan was the Falcons' offensive coordinator before being named head coach of the 49ers.
"My cousin Matt said nothing but great things about Kyle, and I'm excited to get to work with him," said McGlinchey, who was a two-time captain of the Irish team. Kelly also praised McGlinchey on Twitter.
Prospect Profile: Quenton Nelson
Todd McShay says former Notre Dame OG Quenton Nelson can start from day one and be a solid starter for years to come.