The award is presented to an NFL player, coach or staff member who overcomes the most adversity to succeed.
Goodwin notably played through personal anguish last season, as his infant son died from pregnancy complications.
Hours later, Goodwin caught an 83-yard touchdown pass against the New York Giants and broke down in the end zone with his teammates by his side.
Five weeks later, his father died before a game against the Tennessee Titans. Goodwin reeled in a career-high 10 receptions for 114 yards in that contest.
"On behalf of my wife and I, I would like to thank the PFWA for this prestigious award," Goodwin said. "I am so grateful and thankful for all of the support given to us by my teammates, my coaching staff and the 49ers family that helped us get through some of the toughest times in our lives.
"I want all of the people out there that are struggling to remember that the reward lasts longer than the pain."
Los Angeles Chargers wide receiver Keenan Allen, Philadelphia Eagles quarterback Nick Foles, New York Giants offensive tackle Nate Solder and Minnesota Vikings coach Mike Zimmer were also nominated for the 2018 George Halas Award.
Goodwin previously was named as the winner of the Len Eshmont Award, presented annually by the 49ers to the player who best exemplifies inspirational and courageous play. In addition, he also won the Ed Block Courage Award.
The 27-year-old Goodwin recorded career highs in catches (56) and receiving yards (962) to go with two touchdowns last season. He posted two of his three 100-yard games after quarterback Jimmy Garoppolo was inserted as the team's starter.
Goodwin has recorded 105 receptions for 1,702 yards and eight touchdowns in 55 career games with the Buffalo Bills and 49ers.
He was also a member of the 2012 United States Olympic team and a two-time NCAA long jump champion during his career at the University of Texas.