Remarkably, this year's finale features the two franchises who have waited longer than any other to win a championship.
Cleveland's last title came way back in 1948. In ordinary circumstances a win for "the Tribe" would be a baseball fairytale: this year it would mostly be remembered for crushing Chicago's dreams.
The Cubs, despite being one of the most popular and historic franchises in baseball, have not won a World Series title since 1908.
They have not even played in the Fall Classic since 1945, when legend has it that a curse was placed on the team when a local tavern owner was asked to leave a game because the smell of his pet goat was upsetting other fans.
Baseball is fond of hexes. The "Curse of the Bambino" - placed on the Boston Red Sox when they sold Babe Ruth to the New York Yankees - was blamed for the Red Sox's 86-year World Series drought, while the 1920 Black Sox betting scandal was fingered as the reason for the failure of the Cubs' cross-city rivals, the Chicago White Sox, to win a championship for 88 years.
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But the Sox, red and white, finally came good in successive years a decade ago. The Cubs' winless streak stands at 108 years and counting.
Various, possibly more likely, reasons have been advanced for the Cubs' epic failure, including playing more daytime games than most (which some believe denies the players the opportunity to settle into a rhythm), a failure to tap into Latin American talent and a poor system for developing young in-house stars.
Some also believe the innate pessimism of the fans creates a counter-productive atmosphere of tension at their beautiful but capricious Wrigley Field home - where the wind can swirl unpredictably - when things get tense at the business end of the season.
In 2003, the fan effect was more tangible when Steve Bartman covered himself in infamy by impeding a fielder's attempt to catch a key fly ball in a post-season game against the Florida (now Miami) Marlins. Needless to say the Cubs went on to lose the game, and the series and Bartman issued a public letter of apology.
As he puts it on his Twitter feed: "Some people are remembered for a lifetime of great work, I'm remembered for five seconds."
In 2008, a priest even sprinkled holy water in the Cubs' dug-out before their National League Division Series against Los Angeles. They did not win a single game, losing the best-of-five series 3-0.
So why does 2016 finally promise something better?
It seems the key was to make Theo Epstein president of baseball operations in 2011. He is now the highest paid manager in US sport, reportedly on a five-year contract paying more than $50m (£40.87m).
Epstein had already tasted success at the Red Sox, relying on a scientific, analytical method to identify talent. He has repeated the process in Chicago, transforming a team that finished in last place in the National League Central Division for the first three years of his presidency.
The batting line-up was the third most productive in the majors during the regular season.
Dynamic infielders Kris Bryant and Anthony Rizzo both achieved the notable double of driving in more than 100 runs and hitting more than 30 home runs.
But the Cubs' domination of their division, which they won for the first time since 2008 with three weeks of the season still to go, was primarily down to a group of pitchers as daunting as any seen in the major leagues in recent decades.
The key measure of a pitcher's effectiveness is the earned run average (ERA) - the average number of runs they give up during a full nine-inning game. The Cubs' Kyle Hendricks posted the lowest ERA in the major leagues, and team-mate Jon Lester was second.
The Cubs' bullpen - the group of relief pitchers who come into the game in the later stages when the starter has run out of steam - was also among the strongest in baseball.
Sceptics thought the Cubs might again struggle to maintain their form into the postseason, but they eased past the San Francisco Giants 3-1 in the National League Division Series, and then came roaring back from 2-1 down to beat the Los Angeles Dodgers in the NL Championship Series.
Just reaching the World Series prompted scenes of wild celebration.
As David Haugh from the Chicago Tribune put it: "The reaction was visceral, the elation indescribable and the relief undeniable as a crowd of 42,386 fans unleashed 71 years' worth of frustration and disappointment."
The Indians comfortably won the American League Central Division, despite losing their best hitter Michael Brantley to injury for most of the season.
But with injuries to two of their key pitchers, few expected them to beat the Red Sox in the AL Division Series. In fact they swept the Sox, and went on to beat the Toronto Blue Jays in a low-scoring AL Championship Series.
Deftly managed by Terry Francona, who won championships at Boston in 2004 and 2007, the Indians have proved themselves to be consummate battlers this year.
Reaching a World Series is an impressive achievement for a franchise with one of the smallest payrolls in baseball.
But many expect the Cubs to end their years of pain - if they can overcome their internal demons, and a smelly goat.
The Chicago Cubs will be hoping to end the most infamous run of failure in US sport when they face the Cleveland Indians in the World Series, which starts on Tuesday.