In the spring of 2006 Solder signed a letter of intent to attend the University of Colorado, where he played for the Colorado Buffaloes football team from 2006 to 2010. Recruited as a tight end, Solder red-shirted in 2006. In 2007 he played at tight end, catching three passes for 50 yards. As a red-shirt sophomore, Solder was asked to bulk up and shift from tight end to tackle: he quickly won a spot in the starting offensive line, a position he would keep for the rest of his Colorado career, starting every game over the next three seasons. In his junior season: he again started every game, and was named a fourth-team All-American by College Football Insiders. Solder came to Colorado as a redshirt freshman in 2006 as a 6'7", 230-pound tight end; by 2009, he was listed as 6'9", 305 pounds.
Following Christmas 2009, he traveled to Guatemala and volunteered at an orphanage; as a sophomore, he went to Italy during the summer to help rebuild a town after it suffered many collapses from an earthquake. At CU, he regularly participated in the "Read with the Buffs" and "Buffalo Hugs" programs.
Solder signed a contract on August 4, 2011; per the new CBA, it was a four-year deal worth $8.54 million including a $4.7 million signing bonus. Solder played his first regular season game against the Miami Dolphins on September 12, 2011; he allowed just one sack against Pro Bowler Cameron Wake.
Solder was on the active roster for all of the Patriots' games, and started 13 of 16 regular-season games. In some of those games he filled in for right tackle Sebastian Vollmer; when both Vollmer and left tackle Matt Light were healthy, he was used primarily as an additional tight end (making him a tackle eligible). During the regular season, Nate Solder allowed just three sacks, four pressures and 5 penalties on 880 snaps, according to Pro Football Focus.
In 2012, after Light's retirement, Solder became the Patriots' starting left tackle. He started every game of the season, and played 1,234 snaps on offense, the highest of any offensive player in the NFL. Counting special teams, he played 1,339 snaps, second only to fellow Patriots lineman Ryan Wendell.
In the AFC Championship Game, Solder caught his first career pass, resulting in a 16-yard touchdown. Despite an up and down regular season, Solder had an excellent postseason and won his first Super Bowl with the Patriots.