What remains to be seen is whether he'll be summoned to the quaint village of Cooperstown in upstate New York for an encore.
McGwire's 1987 launch in Oakland was punctuated by a home run record for rookies. In St. Louis a decade later, after a frustrating middle act undermined by injuries, his exploration of a new realm culminated in another home run record, this one for the ages.
"Big Mac" was the first man to land on baseball's metaphorical moon: 70 homers in a season.
Tony La Russa, his manager with the Athletics and Cardinals, observed McGwire's evolution from wide-eyed slugger to steely eyed master, a superhero fit for the pages of a comic book.
"He had the greatness of a Hall of Famer," La Russa said. "You know greatness when you see it, and Mark had it."
Both during and after his playing days, however, McGwire became a target of accusations that he was aided by performance-enhancing drugs. His use of androstenedione became a hot topic during his record-breaking season. Legal in professional baseball, andro was banned by other professional sports leagues. When he stopped taking the supplement, McGwire said that he didn't want others to emulate him.
Performance-enhancing drugs have become a major story in baseball, and in the eyes of fans and many voters, McGwire is one of the faces of that abuse, even though he retired before the league began testing for such substances and he has never been proven to have taken anything stiffer than the steroid precursor androstenedione, which was legal at the time.
Critics see such speculation about steroid use as a potential roadblock to his enshrinement. And McGwire's appearance at a Congressional hearing in 2006 in which he refused to talk about his past left a deep impression on both critics and defenders alike.
This is McGwire's first year on the Baseball Writers' Association of America Hall of Fame ballot. A candidate must receive 75 percent of the vote to gain election. Results of the 2007 BBWAA Hall of Fame election will be announced on Jan. 9, and the induction ceremony will take place on July 29 in Cooperstown.
When McGwire came to St. Louis in 1997 in a deal with the A's, having endured a mid-career decline caused by injuries, La Russa admired the finished product -- an athlete at the peak of his powers who galvanized baseball in a magical 1998 season alongside good buddy Sammy Sosa of the Cubs.
"He developed an understanding of what pitchers do to get hitters out," La Russa said. "He loved the confrontation between the pitcher and the hitter."
With Sosa -- who produced 66 homers in '98 -- pushing him all the way, McGwire finished strong and landed on 70, eclipsing the monumental 61 carved out by the Yankees' Roger Maris in 1961.
Dusty Baker's final season as a player was in 1986 in Oakland as McGwire was getting his first taste of big-league life. Baker took a liking to the big, easy-going redhead who would cause him headaches a decade later when Baker managed the Giants.
"Mark's a smart guy -- he learned how to make adjustments after pitchers began to figure him out," Baker said. "He didn't let any weaknesses take away his strength, which is the key for any hitter.
"He was hitting those moon shots right from the start. Later in his career, he was still hitting those moon shots, but he got very selective. He'd wait on one pitch all game -- and not miss it. He was similar to Barry [Bonds] that way."
La Russa has been firm in his resolution that McGwire belongs in Cooperstown with the game's giants.
"Obviously, I'm personally involved in it," La Russa said, "but I hope he gets in sooner than later."
At his peak in 1998 and 1999, McGwire bashed 70 and 65 home runs in back-to-back seasons, driving in 147 runs each season.
Bonds eclipsed McGwire's home run record with 73 in 2001, but McGwire holds the distinction of most homers in back-to-back seasons.
A 12-time All-Star in 16 seasons, "Big Mac" is seventh all-time on the career home run list with 583 and 10th in career slugging percentage at .588. His career on-base percentage is .394.
He averaged 50 homers and 122 RBIs across 162 games.
Five times, he finished among the top seven in Most Valuable Player voting. His highest finish was second in 1998, when Sosa earned the award.
Arriving in Oakland in 1986 off the University of Southern California campus, McGwire settled in as a feared Bash Brother in '87, helping drive the team to three consecutive American League pennants and a World Series title in 1989.
No park could hold him when his 6-foot-5 frame made solid contact, unloading from a unique, crouched stance, bat held high off his right shoulder.
Along with his eye-popping power, McGwire showed uncommon discipline at the plate and sure hands at first base.
He hammered 49 homers in 1987, a record for rookie, and he finished sixth in the AL MVP balloting while claiming the Rookie of the Year Award.
Hindered by a lingering heel injury in 1993 and 1994, McGwire was limited to a total of 74 games and 18 homers. His career seemed to be spinning on a downward plane.
Fighting through back pain, he rebounded with a vengeance in 1995, crushing 39 homers in only 317 at-bats for the highest ratio in history.
Flourishing in Busch Stadium for heartland fans, McGwire endeared himself to the public by inviting the late Roger Maris' family along for the final run to immortality in '98. Big Mac emotionally embraced Maris' offspring in box seats after breaking the record against the Cubs.
"I think he's a Hall of Famer, myself," said San Diego Padres great Tony Gwynn, who heads the ballot along with Cal Ripken Jr. "He hit 500 or so homers, almost 600."
"I think we have no proof whether he did or [did] not [use steroids]."
When he surpassed Maris' 37-year-old record the night of Sept. 8, 1998, McGwire was uncharacteristically ebullient.
"I just give thanks to the man upstairs and all of them -- Roger Maris, Babe Ruth -- everybody who is watching up there," McGwire said. "What a feat."
He'd be thrilled to deliver similar sentiments in Cooperstown someday.
Lyle Spencer is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.