Despite leading Stanford in receiving yards as a senior, Baldwin went undrafted in the 2011 NFL Draft. He signed with the Seattle Seahawks as an undrafted free agent following the end of the 2011 NFL lockout to a three-year deal worth $1.4 million.

Baldwin caught his first career NFL touchdown, a 55-yard reception from quarterback Tarvaris Jackson, in Week 1 of the 2011 season against the San Francisco 49ers, a team which was coached by Jim Harbaugh, Baldwin’s former college coach. He finished fourth in rookie reception yardage in the 2011 NFL season, and led the Seahawks in both receiving yards and receptions. He also made the USA Today All-Joe Team for players who are talented and had put up good numbers, but did not receive a Pro Bowl bid. He became the first undrafted rookie free agent to lead his team in receptions and yards receiving since the AFL-NFL merger.

In the 2012 regular season, Baldwin had 29 receptions for 336 yards and three touchdowns in his first season with quarterback Russell Wilson.

In his third season, Baldwin and the Seahawks had a very successful year. Baldwin caught a career-high five touchdowns in the 2013 season. In the season opener against the Carolina Panthers, he had a season-high seven receptions for 91 receiving yards. Two weeks later, he had his first receiving touchdown of the season, a 35-yard touchdown pass from Tarvaris Jackson, against the Jacksonville Jaguars. On November 3 against the Tampa Bay Buccaneers, he had six receptions for 75 yards and a touchdown. Overall, in the 2013 regular season, he had 50 receptions for 778 yards and five touchdowns. He finished second on the team in receptions and yards.

Baldwin has a video series on YouTube called “Fresh Files”. In the series, he answers questions from fans and talks about recent events in his life. He also talks to other NFL players, most of whom are fellow Seahawks (such as Russell Wilson and Sidney Rice) or Stanford alumni (such as Andrew Luck, Richard Sherman, and Coby Fleener). On November 17, 2013, Baldwin carried the flag of the Philippines onto CenturyLink Field to honor Typhoon Haiyan victims. His grandmother is Filipina and is from Tacloban City. Baldwin is a Christian, and frequently posts about his faith and various Bible verses on his Twitter account. Baldwin is running his own investment firm and serves as an advisor for many organizations in the greater Seattle area.

On March 7, 2014, the Seahawks placed a one-year, second-round tender worth $2.187 million on Baldwin, but he never signed it. Instead, on May 29, Baldwin signed a new two-year, $13 million contract, which included the one-year tender offered to him earlier, making his contract extension three years. Baldwin became the primary receiving threat on the Seahawks after Percy Harvin was traded to the New York Jets.

During the 2015 offseason, the Seahawks acquired Pro Bowl tight end Jimmy Graham from the New Orleans Saints and drafted speedy Kansas State wide receiver Tyler Lockett, giving Baldwin and the Seahawks two more offensive weapons. Baldwin entered training camp as the projected #1 receiver for Seattle. In the season opener against the St. Louis Rams, Baldwin started the season with seven receptions for 35 yards in a 34–31 overtime loss. In Week 2 against the Green Bay Packers Baldwin had seven receptions for 92 yards and one touchdown in a 27–17 loss. In Week 4 against the Detroit Lions, Baldwin had three receptions for 36 yards and a touchdown in a win for the Seahawks.

Baldwin started the 2016 season with a nine-catch, 92-yard outing against the Miami Dolphins, including a three-yard touchdown catch with less than a minute left to secure a narrow 12–10 victory for the Seahawks. Two weeks later against the San Francisco 49ers, Baldwin hauled in eight receptions for then a career-high 164 receiving yards, including a touchdown. In Week 10 on the road against the New England Patriots, he caught six passes for 59 yards, including three touchdowns, equaling a career-high. The following week against the Philadelphia Eagles, he caught four passes for 104 yards and threw his first career touchdown pass on a reverse wide receiver pass to Russell Wilson. Against the Arizona Cardinals in Week 16, he recorded 13 catches for another career-high 171 receiving yards and a touchdown. Much like the 2015 season, Baldwin’s 2016 season was a strong one, and he finished with 94 receptions 1,128 yards and seven touchdowns. In the playoffs, Baldwin continued his strong play. In the Wild Card Round against the sixth-seeded Detroit Lions, Baldwin recorded 11 receptions for 104 yards and a touchdown as the Seahawks defeated the Lions by a score of 26–6. In the Divisional Round, Baldwin again had another strong performance against the second-seeded Atlanta Falcons, catching five passes for 80 yards and a touchdown. However, the Seahawks’ season ended as they fell by a score of 36–20. On January 23, 2017, Baldwin was named to his first career Pro Bowl as an injury replacement for Larry Fitzgerald of the Arizona Cardinals. He was also ranked 88th by his fellow players on the NFL Top 100 Players of 2017.

On May 9, 2019, the Seahawks released Baldwin with a failed physical designation.

On May 12, 2019, Baldwin announced his retirement on Twitter.

Since retiring from the NFL in 2019, Baldwin has joined the board of Valor Worldwide, a Seattle digital media startup and publisher of the Internet property OurMilitary.com, which provides resources and services to the military community. He has also been active in getting his Family First Community Center for the city of Renton, WA off the ground. Baldwin helped establish and currently serves as a board member for the Players Coalition — an NFL player led organization advocating for criminal justice and education reform.