Also an accomplished basketball player, Rudolph played center for his high school team and was the conference player of the year three times and All-Southwest Ohio in 2007. He is currently the second-leading scorer in school history and became just the second Panther to surpass 1,000 career points. He set the school record for most career rebounds when he corralled his 568th rebound on January 11, 2008. Against Moeller (#1 in Ohio, #9 in the nation) on January 25, 2008, he scored 25 of Elder’s 52 points as the Panthers almost upset the top-ranked team in Ohio, 58–52.

Rudolph attended Elder High School in Cincinnati, Ohio, where he played high school football for the Panthers. As a junior, he caught 30 passes for 400 yards and seven touchdowns en route to earning first-team All-city and All-conference honors. As a senior in 2008, he was named first-team All-American by USA Today after totaling 37 receptions for 673 yards (18.2 yards per catch) and 11 touchdowns. He was placed on the Scout.com All-America first team and was the lone tight end among the 11 finalists for the high school Maxwell Award. He received first-team All-Southwest Ohio as a senior after being named second team as a junior and was named second-team All-state by the Associated Press. Following his senior season, Rudolph was invited to play in the 2008 U.S. Army All-American Bowl held in San Antonio, Texas.

As a freshman in 2008, Rudolph became the first tight end in Notre Dame history to start all 13 games as a freshman and the first freshman to ever start a season opener at tight end for Notre Dame. He made his career debut in the season opener against San Diego State and brought in his first career reception for five yards during the victory. In week 3, he posted his first multi-reception game (two catches for 29 yards) of his career against Michigan State, with both catches traveling for 10-plus yards and resulting in first downs against the Spartans. The following week, he hauled in three passes for 32 yards, with a long of 19, while also recording the first touchdown catch of his career in the Irish’ 38-21 win over Purdue. In week 5, he registered season-highs in receptions (5) and receiving yards (70) and added his second and final touchdown of the season versus Stanford. He hauled in two catches for 26 yards against Pittsburgh, setting a new school record for receptions by a freshmen tight end in a single season during the game. In week 11, he established a school record for single-season receiving yards by a freshman tight end during the game against Syracuse. In the 2008 Hawaii Bowl game, he caught four passes for a season-high 78 yards. His 29-yard reception against the Warriors also set a season-best long reception. Rudolph finished his first year with the Irish with 29 receptions for 340 yards (11.7 avg.) and two touchdowns.

As a sophomore in 2009, Rudolph participated in only ten games with nine starts, missing three due to a shoulder injury and totaling 275:59 of playing time while making 57 special-teams appearances. He was named semi-finalist for the John Mackey Award (presented annually to college football’s most outstanding tight end) and was the only sophomore to be named semi-finalist. He hauled in four catches for 29 yards and a touchdown in the opener against Nevada. In week 3, he set a then career-high with 95 receiving yards against Michigan State including a season-long 52-yard reception. His performance against the Spartans earned him John Mackey Tight End of the Week honors. He nabbed touchdown catches in back-to-back weeks against Purdue and Washington, with the first coming against the Boilermakers when there were only 24 seconds remaining in the game on a fourth-and-goal situation that sealed Notre Dame’s win; the second touchdown reception against Washington came with less than two minutes remaining in regulation and gave the Irish the lead. He was voted by his teammates to represent tight ends on the Irish Leadership Committee. Rudolph ended the season ranked third on the team with 33 receptions (17 resulting in first downs) for 364 yards and three touchdowns.

On January 4, 2011, Rudolph decided to forgo his senior season and declared for the 2011 NFL Draft.

Rudolph did not participate in the 2011 NFL combine because of his torn hamstring, but posted a 4.78 40-yard dash time only three weeks after being medically cleared to participate at Notre Dame’s Pro Day in South Bend, Indiana.

In 2012, Rudolph had, in many ways, a breakout year. He was targeted 93 times and had 53 receptions averaging 9.3 yards per reception. Rudolph finished the year with 493 receiving yards and a career-high nine touchdowns, the second-most by a Vikings tight end in a season in team history. His nine touchdown catches, which is a career-high, were also tied for second-most by a tight end in the NFL in 2012. In the season-opener against the Jacksonville Jaguars on September 9, he had a then career-best 67 receiving yards on five receptions. On September 16, he hauled in a six-yard touchdown pass with only 31 seconds remaining in the game versus the Indianapolis Colts to tie the game 20-20 after being down 20-6 entering the 4th quarter of game that Colts won on a late field goal 23-20. In week 3, he had a career-best two touchdown catches in the Vikings’ win at San Francisco, matching the Vikings single-game best by a tight end. In week 6, he caught a touchdown pass and a 2-point conversion pass against the Washington Redskins. The Vikings finished with a 10–6 record and qualified for the playoffs. In the Wild Card Round against the Green Bay Packers, he finished with three receptions for 42 yards in the 24–10 loss.

In 2015, Rudolph started all 16 games for the second time in his career. He posted a career-high 495 yards receiving and had the second-best totals of his career in receptions with 49 and touchdowns with five. Due to a weak Vikings’ offensive line, Rudolph was asked to block often and helped clear the way for Adrian Peterson to lead the NFL in rushing with 1,485 yards on the ground. In Week 2 against the Detroit Lions, he caught 5 passes for 30 yards and a touchdown. Rudolph set a single-game career high with 106 yards receiving against the Green Bay Packers on November 22, including a career-long 47-yard touchdown. The following week, he caught a season-high seven passes in the win against the Atlanta Falcons. In the Wild Card Playoff loss against the Seattle Seahawks, he moved the chains with a 24-yard reception late in the fourth quarter that led to the infamous Blair Walsh’ missed field goal.

In the third preseason game at the U.S. Bank Stadium, Rudolph hauled in a 27-yard touchdown pass from Teddy Bridgewater late in the second quarter. Rudolph’s reception was Minnesota’s first touchdown in its new stadium. In Week 2 of the regular season, Rudolph caught a touchdown pass in the end zone, (the first for Sam Bradford as a Viking) in the 17-14 win over the Green Bay Packers. In the Vikings’ upset of the 2015 NFC champions Carolina Panthers in Week 3, Rudolph was one of the few bright spots for a Vikings’ offense that struggled to move the ball in the first half, catching 7 passes for 70 yards and a touchdown. Against the New York Giants on October 3, Rudolph hauled in five receptions (four of them resulting in first downs) for 55 yards and a touchdown. In Week 13 against the Jacksonville Jaguars, Rudolph hauled in his sixth touchdown of the season and 28th of his career, placing him in a tie with Vikings legend Steve Jordan for the most by a tight end in franchise history. In Week 17 against the Chicago Bears, Rudolph saw 15 passes thrown his way, hauling in 11 for 117 yards (including a touchdown) to set the franchise record for most receptions in a season for a tight end with 83. Overall, in the 2016 season, he finished with 83 receptions for 840 yards and seven touchdowns.

In 2017, Rudolph started all 16 games, recording 57 catches for 532 yards and eight touchdowns. The Vikings finished with a 13-3 record atop the NFC North and made it to the NFC Championship. He had a 25-yard touchdown reception on the first drive of the game, which proved to be the Vikings only score as they went on to lose 38-7 to the eventual Super Bowl champion Philadelphia Eagles. On January 22, 2018, he was named to his second Pro Bowl.

In Week 1 of the 2018 season, Rudolph scored a touchdown, his first with new quarterback Kirk Cousins, in the victory over the San Francisco 49ers. In Week 16, against the Detroit Lions, he caught a Hail Mary for a touchdown before the end of the half. On the day, he had nine receptions for 122 yards and two touchdowns in the 27–9 victory. In the 2018 season, he had 64 receptions for 634 yards and scored four touchdowns.

On June 10, 2019, the Vikings signed Rudolph to a four-year, $36 million contract extension. This came after Rudolph was involved in trade rumors throughout the offseason, but with the new deal, it keeps him under contract through the 2023 season.