The 1981 Topps set contains 726 cards. The first eight cards feature the League Leaders series and cards 201-208 feature the record breakers. Cards 661-686 are the team cards and showcase team checklists on the card backs.

The 1981 Topps set is loaded with stars and Hall-of-Famers including: Carl Yastrzemski, Nolan Ryan, Ozzie Smith, Rickey Henderson, Eddie Murray, Robin Yount, George Brett, Johnny Bench, Mike Schmidt, Reggie Jackson, Paul Molitor, Tom Seaver, Willie Stargell, Joe Morgan, Jim Palmer, Rod Carew, Fergie Jenkins, Gaylord Perry, Rollie Fingers, Steve Carlton, Phil Niekro, Don Sutton, Sparky Anderson, Kirk Gibson, Harold Baines, Carlton Fisk, Tony Perez, Dave Winfield, Gary Carter, Eddie Murray, Dennis Eckersley, Bruce Sutter, Goose Gossage, Dick Williams and Pete Rose